U.S. patent application number 10/507322 was filed with the patent office on 2006-01-19 for absorbent hydrogels.
Invention is credited to Susana Sainz Garcia, Richard Hoskins, Hugh Semple Munro.
Application Number | 20060015083 10/507322 |
Document ID | / |
Family ID | 28045957 |
Filed Date | 2006-01-19 |
United States Patent
Application |
20060015083 |
Kind Code |
A1 |
Munro; Hugh Semple ; et
al. |
January 19, 2006 |
Absorbent hydrogels
Abstract
The invention provides absorbent hydrogel compositions and
hydrogel-containing structures. Typically, a first portion of the
novel materials comprises a porous flexible plasticised hydrophilic
polymer matrix having an internal cellular structure, and a second
portion is relatively non-porous, e.g. comprises a flexible
plasticised hydrophilic polymer matrix having relatively continuous
internal structure. Methods for the manufacture or such hydrogels
and structures are provided, as well as uses thereof.
Inventors: |
Munro; Hugh Semple;
(Chipping Campden, GB) ; Hoskins; Richard;
(Swindon, GB) ; Garcia; Susana Sainz;
(Oxfordshire, GB) |
Correspondence
Address: |
Min Hsieh & Hack;c/o PortfolioIP
P O Box 52050
Minneapolis
MN
55402
US
|
Family ID: |
28045957 |
Appl. No.: |
10/507322 |
Filed: |
March 11, 2003 |
PCT Filed: |
March 11, 2003 |
PCT NO: |
PCT/GB03/01014 |
371 Date: |
June 21, 2005 |
Current U.S.
Class: |
604/367 |
Current CPC
Class: |
A61L 15/60 20130101;
A61L 26/0085 20130101; A61L 24/0036 20130101; A61L 15/425 20130101;
A61L 15/58 20130101; A61L 26/008 20130101; A61L 24/0031
20130101 |
Class at
Publication: |
604/367 |
International
Class: |
A61F 13/15 20060101
A61F013/15 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 11, 2002 |
GB |
0205702.4 |
May 20, 2002 |
GB |
0211529.3 |
Nov 7, 2002 |
GB |
0226066.9 |
Claims
1-39. (canceled)
40. A hydrogel composition comprising a first portion which
comprises a flexible plasticized hydrophilic polymer matrix having
an internal cellular structure, and a second portion which
comprises a flexible plasticized hydrophilic polymer matrix having
relatively continuous internal structure.
41. A hydrogel composition according to claim 40, wherein the first
portion comprises a porous foam having an internal cellular
structure such that the volume ratio of cell void to matrix is
greater than about 1:3.
42. A hydrogel composition according to claim 40, wherein the
second portion has a volume ratio of cell void to matrix less than
about 1:10.
43. A process for the preparation of a porous hydrogel, which
comprises polymerising a polymerisable mixture comprising a
hydrophilic monomer and optionally one or more comonomer, wherein
the polymerisable mixture comprises a first portion including a
relatively high concentration of introduced gas bubbles and a
second portion including a relatively low concentration of gas
bubbles.
44. A process according to claim 43, when used to prepare a
hydrogel composition comprising a first portion which comprises a
flexible plasticized hydrophilic polymer matrix having an internal
cellular structure, and a second portion which comprises a flexible
plasticized hydrophilic polymer matrix having relatively continuous
internal structure.
45. A process according to claim 43, wherein the polymerisable
mixture is laid down in sheet or layer form on a suitable support
arrangement for the polymerization procedure, whereby the first
portion of the polymerisable mixture sits on the second
portion.
46. A porous hydrogel composition comprising a flexible plasticised
hydrophilic polymer matrix having an internal cellular structure,
wherein the hydrophilic polymer is selected from polymers of any of
the following monomers: 2-acrylamido-2-methylpropane sulphonic acid
or a substituted derivative or salt thereof; acrylic acid
(3-sulphopropyl) ester or a substituted derivative or salt thereof;
a non-ionic monomer containing an alkyl or alkylene or substituted
alkyl or alkylene group linked to a carbon-carbon double bond via
an amido or alkylamido function; any mixture of the foregoing with
each other or with one or more comonomer; a monomer/comonomer pair
consisting of a first monomer comprising one or more pendant
anionic group and a second monomer comprising one or more pendant
cationic group; and any mixture of the said monomer/comonomer pair
with any of the foregoing.
47. A porous hydrogel composition according to claim 46, wherein
the non-ionic monomer containing an alkyl or alkylene or
substituted alkyl or alkylene group linked to a carbon-carbon
double bond via an amido or alkylamido function is selected from
diacetone acrylamide, a vinyl lactam, an N-alkylated acrylamide,
and N,N-dialkylated acrylamide, N-vinyl pyrrolidone, N-acryloyl
morpholine, and any mixture thereof.
48. A porous hydrogel composition according to claim 46, wherein,
in the monomer/comonomer pair consisting of a first monomer
comprising one or more pendant anionic group and a second monomer
comprising one or more pendant cationic group, the relative amounts
of the said monomers in the pair are such that the anionic groups
and the cationic groups are present in essentially equimolar
quantities.
49. A porous hydrogel composition according to claim 46, wherein
the monomer is selected from 2-acrylamido-2-methylpropane sulphonic
acid or a salt thereof, acrylic acid (3-sulphopropyl) ester or a
salt thereof, and any mixture thereof.
50. A porous hydrogel composition according to claim 47, wherein
the monomer is N-acryloyl morpholine.
51. A process for the preparation of a porous hydrogel composition
as defined in claim 46, which comprises polymerising a
polymerisable mixture comprising a hydrophilic monomer selected
from said monomers and monomer mixtures, wherein the polymerisable
mixture includes introduced gas bubbles.
52. A process for the preparation of a porous hydrogel composition,
comprising polymerising a polymerisable mixture comprising a
hydrophilic monomer and optionally one or more comonomer, wherein
the polymerisable mixture includes bubbles consisting predominantly
of air, the bubbles having been introduced into the mixture under
an atmosphere consisting predominantly of air, and the mixture
having been laid down for the said polymerisation after
introduction of the bubbles into the polymerisable mixture but
before polymerisation.
53. A process according to claim 52, when used for the preparation
of a hydrogel composition comprising a first portion which
comprises a flexible plasticized hydrophilic polymer matrix having
an internal cellular structure, and a second portion which
comprises a flexible plasticized hydrophilic polymer matrix having
relatively continuous internal structure.
54. A process according to claim 52, wherein the polymerisable
mixture has a bubble to mixture volume ratio greater than about
1:3.
55. A process according to claim 43, wherein the gassed (foamed)
polymerisable mixture is laid down prior to polymerisation in a way
which comprises casting the gassed mixture into sheet form.
56. A bioadhesive article adapted to be adhered to skin in use, the
article comprising an adhesive for contacting the skin and a
substrate supporting the adhesive, wherein the adhesive comprises a
bioadhesive porous plasticized hydrophilic polymer having an
internal cellular structure.
57. The bioadhesive article according to claim 56, wherein the
bioadhesive polymer comprises a hydrogel composition comprising a
first portion which comprises a flexible plasticized hydrophilic
polymer matrix having an internal cellular structure, and a second
portion which comprises a flexible plasticized hydrophilic polymer
matrix having relatively continuous internal structure.
58. The bioadhesive article according to claim 56, wherein the
bioadhesive polymer comprises a hydrogel composition prepared by a
process comprises polymerising a polymerisable mixture comprising a
hydrophilic monomer and optionally one or more comonomer, wherein
the polymerisable mixture comprises a first portion including a
relatively high concentration of introduced gas bubbles and a
second portion including a relatively low concentration of gas
bubbles.
59. A bioadhesive article according to claim 56, wherein the
bioadhesive polymer is present in sheet or layer form.
60. A bioadhesive article according to claim 56, wherein the
bioadhesive polymer is protected by a release layer, the release
layer having been applied to the bioadhesive polymer prior to the
polymerization procedure.
61. A process for preparing a bioadhesive article as defined in
claim 60, wherein prior to the polymerisation the release layer
defines an upper surface of a support arrangement for the
polymerisable mixture, and the polymerisable mixture is laid down
on said release layer.
62. A wound or burn dressing comprising an absorbent member adapted
to contact a wearer's skin in the location of a wound or burn, and
a sheet backing member supporting the absorbent member, the sheet
backing member including a portion which extends beyond the
absorbent member and defines a skin-directed surface which carries
a pressure-sensitive adhesive for securement of the dressing to the
wearer's skin, wherein the said absorbent member comprises a porous
hydrophilic polymer having an internal cellular structure.
63. A wound or burn dressing according to claim 62, wherein the
porous hydrophilic polymer comprises a hydrogel composition
comprising a first portion which comprises a flexible plasticized
hydrophilic polymer matrix having an internal cellular structure,
and a second portion which comprises a flexible plasticized
hydrophilic polymer matrix having relatively continuous internal
structure.
64. A wound or burn dressing according to claim 62, wherein the
porous hydrophilic polymer is prepared by a process comprising
polymerising a polymerisable mixture comprising a hydrophilic
monomer and optionally one or more comonomer, wherein the
polymerisable mixture comprises a first portion including a
relatively high concentration of introduced gas bubbles and a
second portion including a relatively low concentration of gas
bubbles.
65. A wound or burn dressing according to claim 62, wherein the
sheet backing member comprises a foamed polymer, an unfoamed
polymer, a woven natural fibres fabric, a non-woven natural fibres
fabric, a woven synthetic fibres fabric, a non-woven synthetic
fibres fabric, or any combination thereof.
66. A wound or burn dressing according to claim 62, wherein the
pressure sensitive adhesive comprises an acrylic-based polymeric
pressure-sensitive adhesive; a bioadhesive non-porous hydrogel or
gel; or a bioadhesive porous plasticized hydrophilic polymer having
an internal cellular structure.
67. A wound or burn dressing according to claim 66, wherein the
bioadhesive porous plasticized hydrophilic polymer having an
internal cellular structure comprises a hydrogel composition
comprising a first portion which comprises a flexible plasticized
hydrophilic polymer matrix having an internal cellular structure,
and a second portion which comprises a flexible plasticized
hydrophilic polymer matrix having relatively continuous internal
structure.
68. A wound or burn dressing according to claim 66, wherein the
bioadhesive porous plasticised hydrophilic polymer having an
internal cellular structure comprises a hydrogel composition
prepared by a process comprising polymerising a polymerisable
mixture comprising a hydrophilic monomer and optionally one or more
comonomer, wherein the polymerisable mixture comprises a first
portion including a relatively high concentration of introduced gas
bubbles and a second portion including a relatively low
concentration of gas bubbles.
69. A process for the preparation of a hydrogel composition, which
comprises preparing a porous hydrogel composition in sheet or layer
form by polymerising a polymerisable mixture on a suitable support
arrangement to obtain a porous hydrogel composition in sheet or
layer form in which at least the upper face of the sheet or layer
is porous, and applying to the porous upper face of the sheet or
layer, while the sheet or layer is on the support arrangement on
which it was polymerised, a liquid composition comprising the
secondary component of the hydrogel composition or a precursor
thereof, followed by setting, curing or drying of the secondary
component within the porous structure if desired.
70. A process according to claim 69, wherein the application of the
liquid composition comprising the secondary component of the
hydrogel composition or the precursor thereof takes place on the
same day as the polymerisation to form the porous hydrogel
material.
71. A process according to claim 69, wherein any subsequent desired
setting, curing or drying takes place on the same day as the
application of the liquid composition comprising the secondary
component of the hydrogel composition or the precursor thereof.
72. A process according to claim 69, when used for the preparation
of a hydrogel composition comprising a first portion which
comprises a flexible plasticized hydrophilic polymer matrix having
an internal cellular structure, and a second portion which
comprises a flexible plasticized hydrophilic polymer matrix having
relatively continuous internal structure, in which at least some of
the cells contain one or more secondary hydrogel component selected
from electrolytes, pH regulators, colorants, chloride sources,
bioactive compounds such as antimicrobials, antibiotics,
antiseptics, haemostatic agents, wound healing agents,
pharmaceuticals and drugs, burn healing agents, skin cooling
agents, skin moisturizing agents, and skin warming agents, aroma
agents, perfumes, fragrances, scents, polymers, and natural,
synthetic and semi-synthetic gel materials.
73. A porous hydrogel material having an internal cellular
structure and containing within at least some of the cells one or
more secondary hydrogel component selected from electrolytes, pH
regulators, colorants, chloride sources, bioactive compounds such
as antimicrobials, antibiotics, antiseptics, haemostatic agents,
wound healing agents, pharmaceuticals and drugs, burn healing
agents, skin cooling agents, skin moisturizing agents, and skin
warming agents, aroma agents, perfumes, fragrances, scents,
polymers, and natural, synthetic and semi-synthetic gel
materials.
74. A porous hydrogel material according to claim 73, wherein the
internal cellular structure comprises cell walls formed of a
hydrogel composition comprising a first portion which comprises a
flexible plasticized hydrophilic polymer matrix having an internal
cellular structure, and a second portion which comprises a flexible
plasticized hydrophilic polymer matrix having relatively continuous
internal structure
75. A porous hydrogel material according to claim 73, wherein the
internal cellular structure comprises cell walls formed of a
hydrogel composition prepared by a process comprising polymerising
a polymerisable mixture comprising a hydrophilic monomer and
optionally one or more comonomer, wherein the polymerisable mixture
comprises a first portion including a relatively high concentration
of introduced gas bubbles and a second portion including a
relatively low concentration of gas bubbles.
76. A water-absorbent structure comprising a porous hydrogel
portion which comprises a flexible plasticized hydrophilic polymer
matrix having a predominantly open-cell internal cellular
structure, and a relatively non-porous further portion underlying
the porous hydrogel portion, wherein the porous hydrogel portion
comprises a sheet or layer of thickness less than about 0.7 mm.
77. A water-absorbent structure according to claim 76, wherein the
relatively non-porous further portion underlying the porous
hydrogel portion comprises the same hydrogel material as the porous
portion.
78. A water-absorbent structure according to claim 76, wherein the
relatively non-porous further portion underlying the porous
hydrogel portion comprises a different hydrogel material, a
non-hydrogel material, or any combination of these materials.
79. A water-absorbent structure according to claim 76, wherein the
flexible plasticized hydrophilic polymer matrix having a
predominantly open-cell internal cellular structure comprises a
hydrogel composition comprising a first portion which comprises a
flexible plasticized hydrophilic polymer matrix having an internal
cellular structure, and a second portion which comprises a flexible
plasticized hydrophilic polymer matrix having relatively continuous
internal structure.
80. A water-absorbent structure according to claim 76, wherein the
flexible plasticized hydrophilic polymer matrix having a
predominantly open-cell internal cellular structure comprises a
hydrogel composition prepared by a process comprising polymerising
a polymerisable mixture comprising a hydrophilic monomer and
optionally one or more comonomer, wherein the polymerisable mixture
comprises a first portion including a relatively high concentration
of introduced gas bubbles and a second portion including a
relatively low concentration of gas bubbles.
81. A process for the preparation of a hydrogel structure
comprising a porous hydrogel portion which comprises a flexible
plasticised hydrophilic polymer matrix having a predominantly
open-cell internal cellular structure, and a relatively non-porous
further portion underlying the porous portion, wherein the porous
hydrogel portion is in the form of a sheet or layer of thickness
less than about 0.7 mm, the process comprising forming by admixture
of the ingredients a polymerisable mixture comprising one or more
monomer, a curing system for the monomer(s), at least one
surfactant and at least one plasticiser, the mixture including
introduced gas bubbles, and polymerizing the polymerisable mixture,
wherein during the forming of the polymerisable mixture at least
some of the ingredients are mixed together using a rotary mixer
moving forward at a speed of more than about 500 rpm.
82. A process according to claim 81, when used to prepare a
hydrogel composition comprising a first portion which comprises a
flexible plasticized hydrophilic polymer matrix having an internal
cellular structure, and a second portion which comprises a flexible
plasticized hydrophilic polymer matrix having relatively continuous
internal structure
83. A process according to claim 81, when used to prepare a
water-absorbent structure comprising a porous hydrogel portion
which comprises a flexible plasticized hydrophilic polymer matrix
having a predominantly open-cell internal cellular structure, and a
relatively non-porous further portion underlying the porous
hydrogel portion, wherein the porous hydrogel portion comprises a
sheet or layer of thickness less than about 0.7 mm.
84. A process according to 43, wherein at least one further monomer
or other desired component or components of the hydrogel
composition or water-absorbent structure or precursor thereof is
added as a liquid to the polymerisable mixture after it has been
laid down on a suitable support arrangement and before
polymerisation, the conditions being such that the at least one
further monomer or other desired component or components or
precursor percolates through an upper foam layer of the
polymerisable mixture and mixes preferentially into a relatively
bubble-free layer of the polymerisable mixture underlying the foam
layer.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to absorbent (porous)
hydrogels, and more particularly to hydrogels suitable for use in
wound and burn dressings and other applications where a relatively
high speed of fluid uptake is required. The invention also relates
to processes for the manufacture of the novel hydrogels, and to
uses of the hydrogels.
[0002] The expressions "hydrogel" and "hydrogel compositions" used
herein are not to be considered as limited to gels which contain
water, but extend generally to all hydrophilic gels and gel
compositions, including those containing organic non-polymeric
components in the absence of water.
BACKGROUND OF THE INVENTION
[0003] U.S. Pat. No. 5,750,585 (Park et al), the disclosure of
which is incorporated herein by reference, describes certain
superabsorbent hydrogel foams comprising a solid phase and a gas
phase, in which the volume of the gas phase exceeds the volume of
the solid phase. Such foams may generally be thought of as
relatively light foams. The preferred density of the foams is
stated to be between 0.015 and 0.5. Higher densities are stated to
be undesirable as the swelling of the foam is slower (prior art,
column 7, lines 35 to 46).
[0004] The prior art foams are stated to have potential utility as
superabsorbents, oral drug delivery vehicles and gastric retention
devices for diet control.
[0005] Hydrogel foams of polyacrylamide, polyvinylpyrrolidone,
poly-(2-hydroxyethyl-methacrylate) or
poly-(2-hydroxypropyl-methacrylate) are specifically mentioned.
[0006] The particular foams described in the said prior art
document do not contain any organic plasticiser and are dried to
provide superabsorbency. They are generally formed by polymerising
at least one suitable hydrophilic olefin monomer compound in an
aqueous solution containing a surfactant and about 0.1 to about 10%
by weight of a crosslinking agent having at least two alkenyl
groups; introducing gas into the monomer solution during the
polymerisation step to form the foamed polymer matrix; and drying
the foam.
[0007] The Examples of the said prior art patent show the use of
sodium bicarbonate as a carbon dioxide blowing agent to generate
the gas, although the general description mentions also mechanical
introduction of gas into the monomer solution. The introduction of
gas into the monomer solution during the polymerisation step is
inconvenient, and would generally limit the polymerisation
procedure to small batchwise production.
[0008] The foams described in U.S. Pat. No. 5,750,585 swell slowly
on contact with water, typically over a time period of about 1 to 3
hours (see the Figures in the prior art patent). This slowness of
water uptake makes the foams unsuitable for use in the applications
contemplated in the present invention. The relatively low density
of the foam makes it unsuitable for forming into films and sheets
having acceptable mechanical strength.
[0009] U.S. Pat. No. 6,136,873 (Hahnle et al), the disclosure of
which is incorporated herein by reference, describes certain
superabsorbent hydrogel foams. The preferred density of the foam is
stated generally to be between 0.05 and 0.7 g/cm.sup.3.
[0010] The prior art foams are stated to have potential utility as
superabsorbents in diapers, sanitary towels and incontinence
articles, and in certain other conventional uses for
superabsorbents. Dressing material for covering wounds is mentioned
as one potential application (column 15, lines 24 to 26).
[0011] The prior art document contains extensive lists of possible
monomers and monomer mixtures for use in the polymerisable mixture.
However, all the examples use a mixture of acrylic acid and sodium
acrylate.
[0012] The particular foams described in the said prior art
document may contain certain plasticisers and are stated to be
usually dried after polymerisation, preferably to a water content
of between 15 to 35% by weight.
[0013] The gas introduced into the monomer mixture is stated to be
"fine bubbles of a gas inert to free radicals". Examples show the
use of mechanical stirring under an atmosphere of argon or carbon
dioxide.
[0014] The foams described in U.S. Pat. No. 6,136,873 swell on
contact with water, the absorption speed being reported as the
parameter AS in the Examples. As used therein, AS=20/t, where t=the
time for a 1 g piece of the foam to absorb 20 g of water (i.e. a
2000% uptake). While the water uptake rate appears to be faster
than the foams reported in U.S. Pat. No. 5,750,585, the
manufacturing process is inconvenient in view of the need for an
inert gas atmosphere, and is most suitable only for batchwise
production.
[0015] A large amount of research has been conducted into unfoamed,
relatively non-porous, hydrogels based on hydrophilic polymers,
e.g. for use as skin adhesives for a range of applications in
skin-adhesive articles. Such materials exhibit a range of
properties which make them suitable for skin adhesives.
Representative references include PCT Patent Applications Nos.
WO-97/24149, WO-97/34947, WO-00/06214, WO-00/06215, WO-00/07638,
WO-00/46319, WO-00/65143 and WO-01/96422, the disclosures of which
are incorporated herein by reference.
BRIEF DESCRIPTION OF THE INVENTION
[0016] The present invention is based on our surprising finding
that porous hydrogels can be made in a convenient manner with very
acceptable water uptake speeds. The manufacturing process,
particularly at the polymerisation stage, can be batchwise,
partially continuous or continuous. The porous hydrogels can be
prepared in sheet or layer form. The porous hydrogels are
characterised by an internal cellular structure. The porous
hydrogels can combine the requirements of good mechanical strength
and good fluid absorption capacity, optionally also with gel
flexibility and skin tackiness.
[0017] The expressions "comonomer", "monomer" and like expressions
used herein include ionic and non-ionic monomers and monomer
mixtures. The expressions "polymerise", "polymers" and like
expressions include both homopolymerisation and copolymerisation,
and the products thereof.
[0018] According to a first aspect of the present invention, there
is provided a hydrogel composition comprising a first portion which
comprises a flexible plasticised hydrophilic polymer matrix having
an internal cellular structure, and a second portion which
comprises a flexible plasticised hydrophilic polymer matrix having
relatively continuous internal structure.
[0019] The first portion may comprise a porous foam having an
internal cellular structure such that the volume ratio of cell void
to matrix is greater than about 1:3, more preferably greater than
about 1:1, and the second portion may comprise a relatively
non-porous matrix, which may have substantially no cell voids or
only occasional cell voids (e.g. a volume ratio of cell void to
matrix less than about 1:10, for example less than about 1:20). The
said second portion of the hydrogel composition will be referred to
herein as "continuous", which expression is used in the relative
sense explained above.
[0020] It is preferred that the said first, relatively porous,
portion of the hydrogel composition has a first water uptake rate
and the said second, relatively non-porous, portion of the hydrogel
composition has a second water uptake rate which is less than the
first. The first water uptake rate may be very fast, e.g.
comparable with the rate of absorption of water by absorbent paper
kitchen roll. The absorption capacity of the hydrogel composition
will generally be at least about 30% by weight (i.e. the weight of
water taken up and held at saturation will be at least about 30% of
the weight of the hydrogel composition used), and may be as much as
about 20000%. More typically, the absorption capacity of the
hydrogel composition will be between about 300% and about 10000%.
For convenience, the said first portion of the hydrogel composition
will be referred to herein as "porous", which expression is used in
the relative sense explained above.
[0021] According to a second aspect of the present invention, there
is provided a process for the preparation of a porous hydrogel,
e.g. a hydrogel foam, which comprises polymerising a polymerisable
mixture comprising a hydrophilic monomer and optionally one or more
comonomer, wherein the polymerisable mixture comprises a first
portion including a relatively high concentration of introduced gas
bubbles and a second portion including a relatively low
concentration of gas bubbles. When used to prepare the hydrogel
composition according to the first aspect of the invention, the
said first portion of the polymerisable mixture forms the porous
portion of the hydrogel composition after polymerisation, and the
said second portion of the polymerisable mixture forms the
continuous portion of the hydrogel composition after
polymerisation. The first portion of the polymerisable mixture
preferably has a bubble to mixture volume ratio greater than about
1:3, more preferably greater than about 1:1, and the second portion
of the polymerisable mixture preferably has substantially no
bubbles or only occasional bubbles (e.g. a volume ratio of bubbles
to mixture less than about 1:10, for example less than about
1:20).
[0022] The polymerisation step in the process according to the
second aspect of the present invention is preferably a free radical
polymerisation performed in air using a polymerisation inducing
device such as a heat, light (e.g. UV light) or other radiation
source which is in relative motion with respect to the
polymerisable mixture. In this way, a moving line-wise
polymerisation procedure can take place, rather than the static
batchwise procedures available from the prior art. The
polymerisable mixture is preferably laid down in sheet or layer
form on a suitable support arrangement for the polymerisation
procedure, whereby the first portion of the polymerisable mixture
typically sits on the second portion in the manner of a "head" on
beer.
[0023] Certain porous hydrogel compositions are novel per se, and
they and the preferred process for their preparation constitute
further aspects of the present invention.
[0024] According to a third aspect of the present invention, there
is provided a porous hydrogel composition comprising a flexible
plasticised hydrophilic polymer matrix having an internal cellular
structure, wherein the hydrophilic polymer is selected from
polymers of any of the following monomers: [0025]
2-acrylamido-2-methylpropane sulphonic acid or a substituted
derivative or salt thereof; [0026] acrylic acid (3-sulphopropyl)
ester or a substituted derivative or salt thereof; [0027] a
non-ionic monomer containing an alkyl or alkylene or substituted
alkyl or alkylene group linked to a carbon-carbon double bond via
an amido or alkylamido function (e.g. diacetone acrylamide, a vinyl
lactam, an N-alkylated acrylamide, an N,N-dialkylated acrylamide,
N-vinyl pyrrolidone or N-acryloyl morpholine); [0028] any mixture
of any of the foregoing with each other or with one or more
comonomer; [0029] a monomer/comonomer pair consisting of a first
monomer comprising one or more pendant anionic group and a second
monomer comprising one or more pendant cationic group, preferably
such a pair in which the relative amounts of the said monomers in
the pair are such that the anionic groups and the cationic groups
are present in essentially equimolar quantities; [0030] any mixture
of the said monomer/comonomer pair with any of the foregoing.
[0031] The porous hydrogel composition according to the third
aspect of the present invention may comprise a porous foam having
an internal cellular structure such that the volume ratio of cell
void to matrix is greater than about 1:3, more preferably greater
than about 1:1.
[0032] It is preferred that the said porous hydrogel composition
has a very fast water uptake rate, e.g. comparable with the rate of
absorption of water by absorbent paper kitchen roll. The absorption
capacity of the hydrogel composition will generally be at least
about 30% by weight (i.e. the weight of water taken up and held at
saturation will be at least about 30% of the weight of the hydrogel
composition used), and may be as much as about 20000%. More
typically, the absorption capacity of the hydrogel composition will
be between about 300% and about 10000%.
[0033] According to a fourth aspect of the present invention, there
is provided a process for the preparation of a porous hydrogel
composition according to the third aspect of the present invention,
which comprises polymerising a polymerisable mixture comprising a
hydrophilic monomer selected from monomers and monomer mixtures
recited in the third aspect of the present invention, wherein the
polymerisable mixture includes introduced gas bubbles.
[0034] Certain aspects of such a manufacturing process are more
generally novel and inventive.
[0035] According to a fifth aspect of the present invention, there
is provided a process for the preparation of a porous hydrogel
composition, and porous hydrogel compositions prepared thereby, the
process comprising polymerising a polymerisable mixture comprising
a hydrophilic monomer and optionally one or more comonomer, wherein
the polymerisable mixture includes bubbles consisting predominantly
of air, the bubbles having been introduced into the mixture under
an atmosphere consisting predominantly of air, and the mixture
having been laid down for the said polymerisation after
introduction of the bubbles into the polymerisable mixture but
before polymerisation.
[0036] It is particularly preferred that the fourth and fifth
aspects of the present invention are employed in combination.
[0037] The polymerisable mixture in the fourth and fifth aspects of
the present invention preferably has a bubble to mixture volume
ratio greater than about 1:3, more preferably greater than about
1:1.
[0038] The polymerisation step in the process according to the
fourth and fifth aspects of the present invention is preferably a
free radical polymerisation performed in air using a polymerisation
inducing device such as a heat, light (e.g. UV light) or other
radiation source which is in relative motion with respect to the
polymerisable mixture. In this way, a moving line-wise
polymerisation procedure can take place, rather than the static
batchwise procedures available from the prior art. The
polymerisable mixture is preferably laid down in sheet or layer
form on a suitable support arrangement for the polymerisation
procedure.
[0039] The procedures of laying down the gassed (foamed)
polymerisable mixture preferably comprises casting the gassed
mixture into the form of a relatively thin sheet, e.g. up to about
8 mm thick.
[0040] According to a sixth aspect of the present invention, there
is provided a bioadhesive article adapted to be adhered to skin in
use, the article comprising an adhesive for contacting the skin and
a substrate supporting the adhesive, wherein the adhesive comprises
a bioadhesive porous plasticised hydrophilic polymer having an
internal cellular structure. The polymer may preferably be the
hydrogel composition according to the first or third aspect of the
present invention, or prepared according to the second, fourth or
fifth aspect of the present invention, and is preferably in sheet
or layer form. Where the hydrophilic polymer is a hydrogel
composition in accordance with the first aspect of the present
invention, the said continuous portion of the hydrogel composition
will preferably form the skin-contacting surface of the adhesive.
The skin-contacting portion of the hydrogel composition is
preferably overlain with a protective flexible release layer prior
to use of the article. At the time of use, the release layer is
peeled away and may be discarded.
[0041] Most generally, a release layer is suitably applied to the
hydrogel/adhesive polymer layer prior to the polymerisation
procedure, e.g. by the release layer providing an upper surface of
the support arrangement for the polymerisable mixture, onto which
the polymerisable mixture is laid down.
[0042] The porous hydrophilic polymer or hydrogel composition used
in this invention may be electrically conductive and constitute a
skin-contacting adhesive portion of a biomedical electrode. Such a
polymer will typically provide good current dispersion over the
skin-electrode interface.
[0043] A bioadhesive wound or burn dressing typically comprises an
absorbent member adapted to contact a wearer's skin in the location
of a wound or burn, and a sheet backing member supporting the
absorbent member, the sheet backing member including a portion
which extends beyond the absorbent member and defines a
skin-directed surface which carries a pressure-sensitive adhesive
for securement of the dressing to the wearer's skin.
[0044] According to a seventh aspect of the present invention,
there is provided a wound or burn dressing comprising an absorbent
member adapted to contact a wearer's skin in the location of a
wound or burn, and a sheet backing member supporting the absorbent
member, the sheet backing member including a portion which extends
beyond the absorbent member and defines a skin-directed surface
which carries a pressure-sensitive adhesive for securement of the
dressing to the wearer's skin, wherein the said absorbent member
comprises a porous hydrophilic polymer having an internal cellular
structure. The porous hydrophilic polymer may preferably be the
hydrogel composition according to the first or third aspect of the
present invention, or prepared according to the second, fourth or
fifth aspect of the present invention, and is preferably in sheet
or layer form. Where the hydrophilic polymer is a hydrogel
composition in accordance with the first aspect of the present
invention, the said continuous portion of the hydrogel composition
will preferably form the skin-contacting surface of the absorbent
member.
[0045] The sheet backing member is formed of any suitable material,
e.g. a polymer (which may be foamed or unfoamed, or any combination
thereof) such as polyurethane, or a fabric (which may comprise
natural fibres, synthetic fibres or any combination thereof, and
may be woven or non-woven). The sheet backing member may have any
suitable structure, e.g. a web, film, sheet, net or any combination
thereof
[0046] The pressure-sensitive adhesive is any suitable
skin-compatible adhesive, e.g. an acrylic-based polymeric
pressure-sensitive adhesive; a bioadhesive hydrogel or gel such as
those described in the PCT Patent Applications mentioned above; or
a bioadhesive porous plasticised hydrophilic polymer having an
internal cellular structure, such as the hydrogel composition
according to the first or third aspects of the present
invention.
[0047] The skin-contacting adhesive parts of the dressing are
preferably overlain with a protective flexible release layer prior
to use of the dressing. At the time of use, the release layer is
peeled away and may be discarded.
[0048] The porous hydrogel material in accordance with the present
invention has a further utility deriving from its relatively rapid
rate of absorption of liquids. This utility relates to the ability
of the material to imbibe secondary components of a desired end
product, which may be brought into contact, in liquid form, with
the hydrogel material during the manufacturing process. Because of
the speed of absorption achieved, such imbibing of secondary
components can take place immediately or shortly after the
polymerisation, preferably while the hydrogel is still on the same
support arrangement as it was when polymerisation took place.
[0049] Such secondary hydrogel components may include, for example,
liquid dispersions or solutions of conventional additives for
hydrogels, such as electrolytes, pH regulators, colorants, chloride
sources, bioactive compounds such as antimicrobials, antibiotics,
antiseptics, haemostatic agents (such as calcium salts), wound
healing agents, pharmaceuticals and drugs, burn healing agents,
skin cooling agents, skin moisturizing agents, and skin warming
agents, aroma agents, perfumes, fragrances and scents.
[0050] The secondary hydrogel component may also comprise polymer
precursors in liquid form, such as dispersions or solutions of
monomers or monomer mixtures in association with curing systems, or
molten or dispersed or dissolved liquid forms of polymers or other
(e.g. natural, synthetic or semi-synthetic) gel materials such as
alginates (e.g. calcium alginate). When such secondary hydrogel
components are added to the formed porous hydrogel of the present
invention, e.g. immediately or shortly after polymerisation, the
liquid is rapidly taken up into the cellular structure, where it
may be dried, cured or set to create a secondary gel within the
voids of the cellular structure. In the case of an open-cell
structure of the hydrogel, the secondary gel may have relatively
continuous domains within the structure, corresponding to the
connectivity of the cellular structure. The secondary structure can
be used in this way to increase the mechanical strength of the
hydrogel material.
[0051] According to an eighth aspect of the present invention,
there is provided a process for the preparation of a hydrogel
composition, which comprises preparing a porous hydrogel
composition in sheet or layer form by polymerising a pre-gel
mixture on a suitable support arrangement with the upper face of
the sheet or layer being porous, and applying to the porous upper
face of the sheet or layer, while the sheet or layer is on the
support arrangement on which the pre-gel mixture was polymerised, a
liquid composition comprising a secondary component of the hydrogel
composition or a precursor thereof, followed by setting, curing or
drying of the secondary component within the porous structure if
desired. It is preferred that the application of the liquid
composition comprising the secondary component of the hydrogel
composition or the precursor thereof will take place on the same
day as the polymerisation to form the porous hydrogel material,
most preferably within about three hours, e.g. up to about 90
minutes, after the polymerisation, and the any subsequent desired
setting, curing or drying will take place on the same day as the
application of the liquid composition comprising the secondary
component of the hydrogel composition or the precursor thereof,
most preferably within about three hours, e.g. up to about 90
minutes, after the said application.
[0052] The hydrogel material so formed can then be packed and
sealed in conventional manner, or may be further processed, e.g.
into a manufactured article comprising the hydrogel, in
conventional manner or as described herein, before packing and
sealing. By performing the post-imbibing procedure in situ
immediately or soon after the polymerisation of the porous
hydrogel, the manufacturing process can be considerably simplified,
and the chances of bacterial infection or dirt contamination of the
hydrogel material considerably reduced, in view of the increased
potential for automation and the potential for reduction of human
involvement and handling of the product.
[0053] According to a ninth aspect of the present invention, there
is provided a porous hydrogel material having an internal cellular
structure and containing within at least some of the cells one or
more secondary hydrogel component selected from electrolytes, pH
regulators, colorants, chloride sources, bioactive compounds such
as antimicrobials, antibiotics, antiseptics, haemostatic agents
(such as calcium salts), wound healing agents, pharmaceuticals and
drugs, burn healing agents, skin cooling agents, skin moisturizing
agents, and skin warming agents, aroma agents, perfumes,
fragrances, scents, polymers, and other (e.g. natural, synthetic or
semi-synthetic) gel materials such as alginates (e.g. calcium
alginate).
[0054] The preferences for components, manufacturing methods and
uses of the hydrogel materials described herein apply equally to
hydrogel materials formed by the method of the eighth aspect of the
present invention and the hydrogel materials according to the ninth
aspect of the present invention.
[0055] In connection with the present invention, we have also found
that a porous portion (layer) of the porous hydrogel material
described herein, having an internal structure comprising a
predominantly open-cell foam, can by suitable control of the
manufacturing processes be made especially thin, for example less
than about 0.7 mm in thickness, e.g. less than about 0.5 mm in
thickness.
[0056] Surprisingly, we have found that when a porous layer of an
ionic sheet hydrogel is made thin, and especially when the thin
open-celled hydrogel material is underlain by an essentially
non-porous layer, the swelling behaviour of the overall structure
on imbibing of an external liquid is modified, and in particular
the tendency to swell substantially in the direction orthogonal
(normal) to the plane of the sheet (the so-called "z-direction",
this expression deriving from the conventional naming of the
dimensions in a three-dimensional mathematical model) is
significantly reduced. This creates a porous structure which is
dimensionally constant even when imbibing significant volumes of
external liquid. Such "z-restricted" swelling behaviour is
advantageous in many applications, for example wound and burn care
applications. As the thickness of the open-cell layer of the
hydrogel increases, however, then the extent of swelling normal to
the plane increases. The degree of swelling in the z-direction is
preferably less than about 10% of the total thickness of the
structure. The thickness of the underlying non-porous layer is
preferably greater than 0.05 mm.
[0057] Preferably a 0.1 ml drop of normal saline applied to one
point of the porous surface portion of such a hydrogel will after
one minute spread to an area greater than 45 sq.mm, even more
preferably greater than 70 sq.mm, and even more preferably to
greater than 100 sq.mm.
[0058] The essentially non-porous layer underlying the thin porous
layer may suitably be of the same hydrogel material as the porous
layer, but may alternatively be of a different hydrogel material,
of a non-hydrogel material, or any combination of any of these
materials. The non-porous layer may be a mono-, bi- or multi-layer
structure, and in the case of more than one layer the layers may be
of the same or different materials in relation to each other and to
the porous layer. The non-porous layer and component portions
thereof may typically be continuous, closed-cell, predominantly
closed-cell, or any combination thereof, or any other structure
provided that the porosity to external liquids is substantially
less than that of the thin porous layer.
[0059] Without being bound by theory, it seems that the difference
in porosity between the porous and the non-porous portions causes
fluid placed onto the porous part of a sheet of the hydrogel to
spread laterally in the plane of the sheet (so-called "x,y-spread")
to a greater extent than porous hydrogels possessing a greater
depth of open-cell structure at the surface. In effect, the porous
layer can be considered to "wick" the applied fluid relatively
rapidly away from the point of application, and for some reason not
fully understood this effect seems to overtake any tendency of the
hydrogel to swell. Even with only a very thin open-cell hydrogel
layer, the capacity of an ionic hydrogel to imbibe and hold applied
external water is enormous, so there is ordinarily no danger of
saturation of the porous portion.
[0060] In accordance with a tenth aspect of the present invention,
there is provided a water-absorbent structure comprising a porous
hydrogel portion which comprises a flexible plasticised hydrophilic
polymer matrix having a predominantly open-cell internal cellular
structure, and a relatively non-porous further portion underlying
the porous hydrogel portion, wherein the porous hydrogel portion
comprises a sheet or layer of thickness less than about 0.7 mm.
[0061] The relatively non-porous further portion underlying the
porous hydrogel portion may be of the same hydrogel material as the
porous portion, but may alternatively be of a different hydrogel
material, of a non-hydrogel material, or any combination of any of
these materials. The underlying portion may be present as a layer.
The underlying portion may be a mono-, bi- or multi-layer
structure, and in the case of more than one layer the layers may be
of the same or different materials in relation to each other and to
the porous hydrogel portion. The underlying portion and component
portions thereof may typically be continuous, closed-cell,
predominantly closed-cell, or any combination thereof, or any other
structure provided that the porosity to external liquids is
substantially less than that of the thin porous hydrogel
portion.
[0062] The water-absorbent structure with z-restricted swelling
characteristics may be prepared by a number of methods. Where the
structure consists of a hydrogel haying porous and non-porous
portions, a process similar to that of the second aspect of the
present invention may be used, but with additional control of the
mixing of the ingredients of the polymerisable mixture or some of
them, as described below. Where the structure consists of a
hydrogel porous layer overlying a portion composed of a different
hydrogel material or a non-hydrogel material, the portions may be
prepared separately, the porous layer for example using the process
of the fourth or fifth aspects of the present invention, and the
structure assembled after polymerisation. Again, the formation of
the porous layer may be subject to control of the mixing of the
ingredients of the polymerisable mixture or some of them, as
described below.
[0063] Examples of suitable non-porous non-hydrogel materials for
use as potential non-porous portions of the water-absorbent
structure according to the tenth aspect of the present invention
will be well known to those of ordinary skill in this art. Suitable
non-porous sheet materials bondable to hydrogels include non-porous
synthetic polymer films and sheets, of which many suitable examples
are commercially available.
[0064] In accordance with an eleventh aspect of the present
invention, there is provided a process for the preparation of a
hydrogel structure comprising a porous hydrogel portion which
comprises a flexible plasticised hydrophilic polymer matrix having
a predominantly open-cell internal cellular structure, and a
relatively non-porous further portion underlying the porous
portion, wherein the porous hydrogel portion is in the form of a
sheet or layer of thickness less than about 0.7 mm, the process
comprising forming by admixture of the ingredients a polymerisable
mixture comprising one or more monomer, a curing system for the
monomer(s), at least one surfactant and at least one plasticiser,
the mixture including introduced gas bubbles, and polymerizing the
polymerisable mixture, wherein during the forming of the
polymerisable mixture at least some, preferably most or all, of the
ingredients are mixed together using a rotary mixer, e.g. a
propellor or paddle mixer, moving at a speed of more than about 500
rpm, more especially more than about 550 rpm, for example more than
about 600 rpm, e.g. more than about 650 rpm, more than about 700
rpm, more than about 750 rpm, more than about 800 rpm, more than
about 850 rpm, more than about 900 rpm, more than about 950 rpm or
more than about 1000 rpm.
[0065] Generally speaking, it is found that the higher the speed of
mixing the greater the level of closed-cell hydrogel relative to
open-cell, i.e. the thinner the surface open-cell layer in the
resultant structure. The absolute value of the mixing speed
required will depend in part on the nature and amount of the
surfactant used, and may need to be established through preliminary
tests. Such tests will be well within the capacity of those of
ordinary skill in this art.
[0066] The preferences for components, manufacturing methods and
uses of the hydrogel materials described herein apply equally to
hydrogel materials present in the structures according to the tenth
aspect of the present invention and obtainable by the process
according to the eleventh aspect of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The Hydrogel Composition--Internal Structure
[0067] The internal cellular structure of the porous hydrogel
composition or, when porous and continuous portions are present,
the porous portion of the hydrogel composition, may be closed-cell
throughout, open-cell throughout, or may have regions of
closed-cell structure and regions of open-cell structure. Generally
speaking, an open-cell structure will absorb fluid at a faster
initial rate than a closed-cell structure, by reason of the
interconnection of the internal cells.
[0068] Where porous and continuous portions of the hydrogel
composition are present, they may suitably comprise layers, which
may be of the same or different materials. The layers may be
integrally formed or may be laminated together, optionally with
intermediate bonding media
[0069] The said porous and continuous portions of such a hydrogel
composition are preferably of the same material and integrally
formed in a single polymerisation step.
[0070] In the polymerisation step, to be described in more detail
below, a fluid pre-gel material is preferably gassed with bubbles
of a gas, prior to laying down the pre-gel. The gas is preferably
air. To prepare a hydrogel composition comprising porous and
continuous portions, the lain down pre-gel is then preferably
allowed or assisted to partially "drain", by which is meant that a
certain amount of the pre-gel material is allowed to revert to an
essentially continuous, unfoamed, fluid state to form the second
portion of the polymerisable mixture. By controlling the extent of
draining, the relative thickness of the porous and continuous
portions in the resulting cured hydrogel composition can be
controlled. To prepare a porous hydrogel composition without a
continuous portion, draining is avoided.
[0071] Where the porous and continuous portions of the hydrogel
composition are present and are of different materials, the
portions may suitably also be integrally formed in a single
polymerisation step. We have found that the first (foam) portion of
the laid down polymerisable mixture is usually relatively robust,
and will not collapse if additional ingredients, e.g. comonomers,
are added onto the mixture as a liquid dispersion, solution or
mixture before the polymerisation step. In practice, the added
ingredients percolate down through the first portion of the mixture
and preferentially invade the fluid second portion below. By
controlling the time allowed for this process, a range of
differential-composition multi-layer porous hydrogels can be
prepared conveniently, using a single polymerisation step to
produce essentially the final hydrogel, without the need for
lamination and handling of individual component layers after
polymerisation or for laminar laying down of different
polymerisable mixtures.
The Hydrogel Composition--External Form
[0072] The hydrogel composition may suitably be present in the form
of a sheet having first and second major faces, each of said first
and second major faces being in contact with a protective release
layer, for example siliconised plastic or paper. Alternatively, the
hydrogel composition may be present in the form of a sheet having
first and second major faces, one of said first and second major
faces being in contact with a protective release layer, for example
siliconised plastic or paper, and the other of said first and
second major faces being in contact with apart of a larger article,
e.g. a backing member forming part of a wound or burn dressing, a
biomedical electrode or another article. Particularly preferred are
articles where a bioadhesive hydrogel layer is to be provided in
use between the article and the skin of a patient. Such articles
are exemplified below (see "Applications"). Still further, the
hydrogel composition may be present in the form of a sheet having a
woven or non-woven fabric, or a net, embedded therein.
[0073] The hydrogel sheets may typically have a thickness in the
range of about 0.1 mm to about 10 mm, e.g. about 0.5 mm to about 10
mm. The thickness of the foam or film-foam structure can suitably
be from about 0.1 mm to about 3 mm. When such sheets are in contact
with a release sheet, for example a sheet of plastic or coated
plastic (e.g. siliconised plastic) or paper or coated paper (e.g.
siliconised paper), the hydrogel composition may suitably be coated
at a surface weight of hydrogel in the range of about 0.5
kg/m.sup.2 to about 2.5 kg/m.sup.2.
[0074] For the preparation of a hydrogel composition in the form of
a sheet, the process according to the invention may include
initially forming a sheet of the pre-gel, and subsequently carrying
out the polymerisation step so that the sheet hydrogel is formed in
situ by the polymerisation reaction, as described in more detail
below. In one embodiment, the resultant hydrogel may be used
substantially as made, i.e. material is not substantially added to
or removed from the resultant hydrogel composition, although in
some cases some degree of subsequent conditioning and/or
modification may be desirable, and in addition the post-processing
of the eighth aspect of the present invention may advantageously be
applied.
[0075] When the hydrogel composition contains water, the water may
be present in any suitable amount. The typical range of water
content is between 0 and about 95% by weight of the hydrogel. The
hydrogel composition may conveniently be classified as "high water
content" or "low water content". The expression "high water
content" refers particularly to hydrogel compositions comprising
more than about 40% by weight of water, more particularly above
about 50% by weight, and most preferably between about 60% and
about 95% by weight. The expression "low water content" refers
particularly to hydrogel compositions comprising up to about 40% by
weight of water.
The Hydrogel Composition--Physical Parameters
[0076] The density of the hydrogel compositions of the present
invention can be selected within a wide range, according to the
materials used and the manufacturing conditions.
[0077] Generally speaking, the bulk density of the total hydrogel
composition may be in the range of about 0.05 to about 1.5
g/cm.sup.3, more typically in the range of about 0.3 to about 0.8
g/cm.sup.3.
[0078] The water activity of the hydrogel compositions of the
present invention typically lies within the range of 0 to about
0.96, as measured by an AquaLab Series 3TE water activity
meter.
[0079] The water uptake rate of the hydrogel compositions of the
present invention (or, where the composition includes a portion
which is more porous than another portion, of the more porous
portion) typically lies within the range of at least about 2
.mu.l/s, more preferably between about 2 and about 1001 .mu.l/s, as
measured by the technique of applying a 5 .mu.l drop of water from
a syringe onto the face of the sheet hydrogel and measuring the
reduction in volume of the drop over a period of 0.1 s starting
from contact between the drop and the hydrogel, and extrapolating
to a rate expressed as volume per second, the measurements being
made using a Scientific and Medical Products DAT1100 dynamic
contact angle analyser. A water uptake rate of, say, 25 .mu.l/s,
indicates complete absorption of the applied water in 0.2 s.
[0080] The water uptake rate of the hydrogel compositions of the
first aspect of the present invention from the continuous portion
side is typically less than the rate from the porous portion side,
as measured by the same technique.
[0081] The absorption capacity of the hydrogel composition will
generally be between about 30% and about 20000%. More typically,
the absorption capacity of the hydrogel composition will be between
about 300% and about 10000%.
Preparative Method--General
[0082] According to the invention, the processes for the
preparation of porous hydrogels generally comprise polymerising a
polymerisable mixture comprising at least one hydrophilic monomer,
wherein the polymerisable mixture includes introduced gas bubbles,
preferably, but not limited to, air bubbles.
[0083] In addition to the at least one hydrophilic monomer, a
curing system should be present in the polymerisable mixture. The
curing system typically includes at least one cross-linking agent
and at least one suitable polymerisation initiator.
[0084] In one embodiment, the polymerisable mixture can comprise a
first portion including a relatively high concentration of
introduced gas bubbles and a second portion including a relatively
low concentration of gas bubbles.
[0085] The polymerisation is preferably a free radical
polymerisation of a fluid polymerisable mixture comprising [0086]
(1) a free radically polymerisable hydrophilic monomer, optionally
together with at least one free radically polymerisable comonomer;
and [0087] (2) one or more cross-linking agent comprising a
multifunctional unsaturated free radically polymerisable compound;
the polymerisation being conducted in the presence or absence of a
plasticiser, with the proviso that when the polymerisation is
conducted in the absence of a plasticiser, a plasticiser is added
to the polymer product of the polymerisation.
[0088] The polymerisable mixture (pre-gel) preferably includes the
monomer(s) at a total monomer level of from about 5% to about 70%
by weight of the total mixture, more particularly from about 10% to
about 60% by weight, most preferably from about 15% to about 50% by
weight.
[0089] When the polymerisation is conducted in the presence of a
plasticiser, one or more different plasticiser and/or more of the
same plasticiser may, if desired, be added to the polymer product
of the polymerisation.
[0090] The plasticiser may be selected from aqueous and non-aqueous
systems. Water or a mixture of water and a water-miscible organic
plasticiser may suitably be used as an aqueous plasticiser. When a
non-aqueous plasticiser is used, it may suitably be an organic
plasticiser. Please see below ("Plasticiser"), for more details of
plasticiser systems.
Preparation and Laying Down of the Polymerisable Mixture
[0091] In preparing hydrogel compositions in accordance with the
invention, the ingredients are initially mixed to provide an
ungassed polymerisable reaction mixture in the form of an initial
fluid pre-gel.
[0092] The initial fluid pre-gel is then blown to introduce a gas
into the mixture before polymerization. The gas can be introduced
by mechanical means or by introduction of a blowing agent.
Mechanical means include the use of a high speed blender or
propeller under an atmosphere of the gas, or the introduction of
the gas into the liquid through a capillary, nozzle or microporous
surface. A blowing agent is any substance or combination of
substances capable of producing the gas upon introduction into the
mixture and application of any necessary initiation steps. Examples
of blowing agents include carbonates or metal powders which react
with acidic conditions to generate hydrogen or carbon dioxide, such
as sodium bicarbonate, and chemical agents which liberate gas under
the influence of heat such as dipotassium diazomethionate,
N-nitroso-.beta.-amino-ketones or sodium borohydride. Initiation of
blowing will be achieved in any appropriate way, according to the
chemicals being employed. Such initiation procedures will be well
within the capacity of those skilled in the art.
[0093] The preferred gas for use in the present invention is air,
which is preferably introduced into the initial pre-gel by
mechanical means. To produce uniform cells in the porous portion of
the hydrogel, the air bubbles introduced must be uniformly
dispersed and the dispersion substantially maintained up until the
point of gelation at polymerization.
[0094] The ingredients of the initial pre-gel are preferably
mechanically mixed in such a way as to foam the mixture by the
mechanical introduction of many small air bubbles. A typical mixing
procedure would use a paddle stirrer for up to about 5 minutes at a
paddle speed of up to about 800 rpm.
[0095] The viscosity of the initial pre-gel may need to be
controlled. On the one hand, the viscosity should be low enough to
permit effective introduction of the gas, as described below. On
the other hand, the viscosity should not be so low that all the
introduced gas bubbles rise to the surface and dissipate into the
atmosphere before polymerization can take place to form the
polymeric matrix. However, as explained above, a certain degree of
"draining" is preferred, in order to obtain the hydrogel
composition comprising integra 1 porous and continuous portions in
one polymerization step. We have found that a viscosity of up to
about 1000 mPas, more typically less than about 100 mPas, and most
preferably lass than about 50 mPas (as measured in a Brookfield
Viscometer with a S18 spindle in a closed volume at a speed of 20
rpm) is suitable for the initial pre-gel before introduction of
gas, e.g. between about 10 and about 50 mPas.
[0096] The viscosity of the pre-gel mixture will rise as a result
of this foaming procedure, to a typical range of between about 200
and about 1000 mPas (as measured in a Brookfield Viscometer with a
S18 spindle in a closed volume at a speed of 2 rpm).
[0097] The gassed pre-gel mixture is then preferably laid down
(cast) onto a suitable support arrangement prior to exposure to the
source of the polymerising heat or radiation. The upper surface of
the support arrangement is preferably provided by the sheet that
will constitute the protective release layer to be provided with
the hydrogel composition before use of any article in which it is
included. Further details of a preferred embodiment of this release
layer are given below ("Apparatus").
[0098] In the time delay between casting onto the support
arrangement and irradiation, the foamed pre-gel mixture may be
allowed to "drain", whereby a relatively bubble-free fluid layer
forms under the foam layer, as previously described in connection
with some aspects of the present invention.
[0099] The foam layer is usually mechanically stable enough that at
least one further monomer or other desired component or components
of the hydrogel composition can be added to the pre-gel mixture as
it rests on the support arrangement awaiting polymerisation. Such
additional components are typically applied on top of the foam
layer in the form of a fluid dispersion, mixture or solution, e.g.
in water, which then percolates down through the foam layer and
mixes with any relatively bubble-free fluid layer underneath the
foam. In this way, the composition of a continuous portion of the
final hydrogel composition can be made different from that of the
porous layer of the final composition, in a convenient way which
still requires only one polymerisation step and can avoid or at
least limit the degree of post-polymerisation handling, manufacture
and processing of the product that is required.
[0100] A list of examples of suitable additional components is
given below under the heading "Other Additives".
[0101] The polymerisable mixture is then passed to the
polymerisation step, which will now be discussed.
The Polymerisation Reaction
[0102] Any suitable free radical polymerisation reaction may be
used, according to the monomers present in the pre-gel. The range
of reactions and their appropriate initiation and other conditions
will be well known to those of ordinary skill in this art.
[0103] For example, the free radical polymerisation may be
initiated in generally known manner by light (photoinitiation),
particularly ultraviolet light (UV photoinitiation); heat (thermal
initiation); electron beam (e-beam initiation); ionising radiation,
particularly gamma radiation (gamma initiation); non-ionising
radiation, particularly microwave radiation (microwave initiation);
or any combination thereof. The pre-gel mixture may include
appropriate substances (initiators), at appropriate levels, e.g. up
to about 5% by weight, more particularly between about 0.002% and
about 2% by weight, which serve to assist the polymerisation and
its initiation, in generally known manner.
[0104] In one embodiment, the process of the invention involves
free radical polymerisation and the use of a photoinitiator or a
combination of photo- and other initiation. Preferably the reaction
mixture comprises an amount of photoinitiator of from about 0.003%
to about 0.5%, and particularly from about 0.003% to about 0.4%,
most particularly from about 0.009% to about 0.2%, by weight of the
total polymerisation reaction mixture. If desired, the low levels
of photoinitiator described in WO-01/96422 may be used.
[0105] In one preferred embodiment, the polymerisable mixture and
the source of the polymerization initiator (e.g. the radiation
source) move relative to one another for the polymerization step.
In this way, a relatively large amount of polymerisable material
can be polymerized in one procedure, more than could be handled in
a static system. This moving system is referred to herein as
continuous production, and is preferred.
[0106] Preferred photoinitiators include any of the following
either alone or in combination:
[0107] Type I-.alpha.-hydroxy-ketones and benzilidimethyl-ketals
e.g. Irgacure 651. These are believed on irradiation to form
benzoyl radicals that initiate polymerisation. Photoinitiators of
this type that are preferred are those that do not carry
substituents in the para position of the aromatic ring. Examples
include Irgacure 184 and Daracur 1173 as marketed by Ciba
Chemicals, as well as combinations thereof.
[0108] A particularly preferred photoinitiator is
1-hydroxycyclohexyl phenyl ketone; for example, as marketed under
the trade name Irgacure 184 by Ciba Speciality Chemicals. Also
preferred are Daracur 1173 (2-hydroxy-2-propyl phenyl ketone) and
mixtures of Irgacure 184 and Daracur 1173.
[0109] Photo-polymerisation is particularly suitable, and may be
achieved using light, optionally together with other initiators,
such as heat and/or ionizing radiation. Photoinitiation will
usually be applied by subjecting the pre-gel reaction mixture
containing an appropriate photoinitiation agent to ultraviolet (UV)
light. The incident UV intensity, at a wavelength in the range from
240 to 420 nm, is typically greater than about 10 mW/cm.sup.2. The
processing will generally be carried out in a controlled manner
involving a precise predetermined sequence of mixing and thermal
treatment or history.
[0110] The UV irradiation time scale should ideally be less than 60
seconds, and preferably less than 10 seconds to form a gel with
better than 95% conversion of the monomers. Those skilled in the
art will appreciate that the extent of irradiation will be
dependent on a number of factors, including the UV intensity, the
type of UV source used, the photoinitiator quantum yield, the
amount of monomer present, the nature of the monomer(s) present,
the presence of dissolved oxygen, the presence of polymerisation
inhibitor, the thickness of the reaction mixture when coated onto
the substrate and the nature of substrate onto which the reaction
mixture is coated.
[0111] After completion of the polymerisation reaction, and after
any desired post-processing (such as provided by the eighth aspect
of the present invention, described above), the hydrogel
composition may typically be used immediately in a manufacturing
procedure, e.g. to provide a skin-adhesive layer in an article, or
a top release layer may be applied to the porous top side of the
polymerised sheet material for storage and transportation of the
porous hydrogel sheet.
Apparatus
[0112] The apparatus used is generally conventional and
commercially available.
[0113] As mentioned above, however, according to one aspect of the
present invention the support arrangement on which the gassed
polymerisable mixture is laid down preferably supports, and thereby
presents as its upper surface, the release layer.
[0114] In one preferred embodiment, the release layer is formed of
a plastic sheet material, such as a polyolefin (e.g. polyethylene).
The plastic material may optionally be coated with a non-stick
material such as a silicone.
Ingredients of the Hydrogel Composition
[0115] The preferred hydrogel composition of the present invention
comprises a plasticised three-dimensional matrix of cross-linked
polymer molecules, and has sufficient structural integrity to be
self-supporting even at very high levels of internal water content,
with sufficient flexibility to conform to the surface contours of
the human skin. Where the intended use of the hydrogel is in
biomedical electrodes, wound dressings, and other applications
where skin adhesion is desired, the hydrogel composition preferably
has sufficient bioadhesion to adhere to the skin under all skin and
moisture conditions likely to be encountered during use. Our PCT
Patent Application No. WO-00/45864, the disclosure of which is
incorporated herein by reference, describes a method whereby the
skin adhesion performance of the hydrogel can be predicted and
thereby tailored to particular applications.
[0116] The hydrogel compositions with which the present invention
is concerned generally comprise, in addition to the cross-linked
polymeric network, an aqueous plasticising medium and, where
electrical conductivity is required, at least one electrolyte,
whilst the materials and processing methods used are normally
chosen to provide a suitable balance of adhesive and electrical
properties for the desired application.
[0117] Ionic Monomers
[0118] The one or more ionic monomer, if present, will be water
soluble and may be selected from: 2-acrylamido-2-methylpropane
sulphonic acid or an analogue thereof or one of its salts (e.g. an
ammonium or alkali metal salt such as a sodium, potassium or
lithium salts); acrylic acid or an analogue thereof or one of its
salts (e.g. an alkali metal salt such as a sodium, potassium or
lithium salt); and/or a polymerisable sulphonate or a salt thereof
(e.g. an alkali metal salt such as a sodium, potassium or lithium
salt), more particularly acrylic acid (3-sulphopropyl) ester or an
analogue thereof, or a salt thereof. The term "analogue" in this
context refers particularly to substituted derivatives of
2-acrylamido-2-methylpropane sulphonic acid, of acrylic acid or of
acrylic acid (3-sulphopropyl) ester.
[0119] A further category of ionic monomer that may be mentioned is
a monomer/comonomer pair consisting of a first monomer comprising
one or more pendant anionic group and a second monomer comprising
one or more pendant cationic group, the relative amounts of the
said monomers in the pair being such that the anionic groups and
cationic groups are present in essentially equimolar quantities.
The said anionic and cationic groups may be selected from groups
which are salts of acid groups and groups which are salts of basic
groups. The pendant groups in the first monomer are preferably the
sodium, potassium, calcium, lithium and/or ammonium (individually
or in any combination of one or more) salts of carboxylic acid,
phosphoric acid and/or sulphonic acid. Sulphonic acid groups are
most preferred. The pendant groups in the second monomer are
preferably quaternary ammonium salts of halide (for example
chloride), sulphate and/or hydroxide. Chloride and sulphate are
most preferred.
[0120] A particularly preferred ionic monomer is a sodium salt of
2-acrylamido-2-methylpropane sulphonic acid, commonly known as
NaAMPS, which is available commercially at present from Lubrizol as
either a 50% aqueous solution (reference code LZ2405) or a 58%
aqueous solution (reference code LZ2405A) and/or acrylic acid
(3-sulphopropyl) ester potassium salt, commonly known as SPA or
SPAK. SPA or SPAK is available commercially in the form of a pure
solid from Raschig. In the case of polymers formable from a
monomer/comonomer pair consisting of a first monomer comprising one
or more pendant anionic group and a second monomer comprising one
or more pendant cationic group, the relative amounts of the said
monomers in the pair being such that the anionic groups and
cationic groups are present in essentially equimolar quantities,
these ionic monomers will provide suitable monomers comprising one
or more pendant anionic group. In that case, suitable monomers
comprising one or more pendant cationic group may, for example, be
alkyl ester derivatives of acrylic acid in which the alkyl group
carries a quaternised ammonium ion substituent, the counter-anion
suitably being halide (for example chloride), sulphate and/or
hydroxide. Acryloyloxyethyltrimethylammonium salts (e.g. the
chloride) are particularly mentioned.
[0121] Non-Ionic Monomers
[0122] The one or more non-ionic monomer, if present, may
preferably be water soluble and be selected from acrylamide or a
mono- or di-N-alkylacrylamide or an analogue thereof. The term
"analogue" in this in this context refers to non-ionic water
soluble monomers containing an alkyl or substituted alkyl group
linked to a carbon-carbon double bond via an amido or alkylamido
(--CO.NH-- or --CO.NR--) function. Examples of such analogues
include diacetone acrylamide
(N-1,1-dimethyl-3-oxobutyl-acrylamide), vinyl lactams, N-alkylated
acrylamides, N,N-dialkylated acrylamides, N-vinyl pyrrolidone,
N-acryloyl morpholine and any mixture thereof. N-acryloyl
morpholine is particularly preferred.
[0123] Cross-Linking Agents
[0124] Conventional cross-linking agents are suitably used to
provide the necessary mechanical stability and to control the
adhesive properties of the hydrogel. The amount of cross-linking
agent required will be readily apparent to those skilled in the art
such as from about 0.01% to about 0.5%, particularly from about
0.05% to about 0.4%, most particularly from about 0.08% to about
0.3%, by weight of the total polymerisation reaction mixture.
Typical cross-linkers include tripropylene glycol diacrylate,
ethylene glycol dimethacrylate, triacrylate, polyethylene glycol
diacrylate (polyethylene glycol (PEG) molecular weight between
about 100 and about 4000, for example PEG400 or PEG600), and
methylene bis acrylamide.
[0125] Organic Plasticisers
[0126] The one or more organic plasticiser, when present, may
suitably comprise any of the following either alone or in
combination: at least one polyhydric alcohol (such as glycerol,
polyethylene glycol, or sorbitol), at least one ester derived
therefrom, at least one polymeric alcohol (such as polyethylene
oxide) and/or at least one mono- or poly-alkylated derivative of a
polyhydric or polymeric alcohol (such as alkylated polyethylene
glycol). Glycerol is the preferred plasticiser. An alternative
preferred plasticiser is the ester derived from boric acid and
glycerol. When present, the organic plasticiser may comprise up to
about 45% by weight of the hydrogel composition.
[0127] Surfactants
[0128] Any compatible surfactant may optionally be used as an
additional ingredient of the hydrogel composition. Surfactants can
lower the surface tension of the mixture before polymerisation and
thus aid processing. Non-ionic, anionic and cationic surfactants
are preferred. The surfactant ideally comprises any of the
surfactants listed below either alone or in combination with each
other and/or with other surfactants. The total amount of
surfactant, if present, is suitably up to about 10% by weight of
the hydrogel composition, preferably from about 0.05% to about 4%
by weight.
1. Non-Ionic Surfactants
[0129] Suitable non-ionic surfactants include, but are not limited
to, those selected from the group consisting of the condensation
products of a higher aliphatic alcohol, such as a fatty alcohol,
containing about 8 to about 20 carbon atoms, in a straight or
branched chain configuration, condensed with about 3 to about 100
moles, preferably about 5 to about 40 moles and most preferably
about 5 to about 20 moles of ethylene oxide. Examples of such
non-ionic ethoxylated fatty alcohol surfactants are the
Tergitol.TM. 15-S series from Union Carbide and Brij.TM.
surfactants from ICI. Tergitol.TM. 15-S surfactants include
C.sub.11-C.sub.15 secondary alcohol polyethyleneglycol ethers.
Brij.TM. 58 surfactant is polyoxyethylene(20) cetyl ether, and
Brij.TM. 76 surfactant is polyoxyethylene(10) stearyl ether.
[0130] Other suitable non-ionic surfactants include, but are not
limited to, those selected from the group consisting of the
polyethylene oxide condensates of one mole of alkyl phenol
containing from about 6 to 1.2 carbon atoms in a straight or
branched chain configuration, with about 3 to about 100 moles of
ethylene oxide. Examples of non-ionic surfactants are the
Igepal.TM. CO and CA series from Rhone-Poulenc. Igepal.TM. CO
surfactants include nonylphenoxy poly(ethyleneoxy) ethanols.
Igepal.TM. CA surfactants include octylphenoxy poly(ethyloneoxy)
ethanols.
[0131] Another group of usable non-ionic surfactants include, but
are not limited to, those selected from the group consisting of
block copolymers of ethylene oxide and propylene oxide or butylene
oxide. Examples of such non-ionic block copolymer surfactants are
the Pluronic.TM. and Tetronic.TM. series of surfactants from BASF.
Pluronic.TM. surfactants include ethylene oxide-propylene oxide
block copolymers. Tetronic.TM. surfactants include ethylene
oxide-propylene oxide block copolymers. The balance of hydrophobic
and hydrophilic components within the surfactant together with the
molecular weight are found to be important. Suitable examples are
Pluronic L68 and Tetronic 1907. Particularly suitable examples are
Pluronic L64 and Tetronic 1107.
[0132] Still other satisfactory non-ionic surfactants include, but
are not limited to, those selected from the group consisting of
sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid
esters and polyoxyethylene stearates. Examples of such fatty acid
ester non-ionic surfactants are the Span.TM., Tween.TM., and
Myrj.TM. surfactants from ICI. Span.TM. surfactants include
C.sub.12-C.sub.18 sorbitan monoesters. Tween.TM. surfactants
include poly(ethylene oxide) C.sub.12-C.sub.18 sorbitan monoesters.
Myrj.TM. surfactants include poly(ethylene oxide) stearates.
2. Anionic Surfactants
[0133] Anionic surfactants normally include a hydrophobic moiety
selected from the group consisting of (about C.sub.6 to about
C.sub.20) alkyl, alkylaryl, and alkenyl groups and an anionic group
selected from the group consisting of sulfate, sulfonate,
phosphate, polyoxyethylene sulfate, polyoxyethylene sulfonate,
polyoxyethylene phosphate and the alkali metal salts, ammonium
salts, and tertiary amino salts of such anionic groups.
[0134] Anionic surfactants which can be used in the present
invention include, but are not limited to those selected from the
group consisting of (about C.sub.6 to about C.sub.20) alkyl or
alkylaryl sulfates or sulfonates such as sodium lauryl sulfate
(commercially available as Polystep.TM. B-3 from Srepan Co.) and
sodium dodecyl benzene sulfonate, (commercially available as
Siponate.TM. DS-10 from Rhone-Poulenc); polyoxyethylene (about
C.sub.6 to about C.sub.20) alkyl or alkylphenol ether sulfates with
the ethylene oxide repeating unit in the surfactant below about 30
units, preferably below about 20 units, most preferably below about
15 units, such as Polystep.TM. B-1 commercially available from
Stepan Co. and Alipal.TM. EP110 and 115 from Rhone-Poulenc; (about
C.sub.6 to about C.sub.20) alkyl or alkylphenoxypoly
(ethyleneoxy)ethyl mono-esters and di-esters of phosphoric acid and
its salts, with the ethylene oxide repeating unit in the surfactant
below about 30 units, preferably below about 20 units, most
preferably below about 15 units, such as Gafac.TM. RE-510 and
Gafac.TM. RE-610 from GAF.
3. Cationic Surfactants
[0135] Cationic surfactants useful in the present invention
include, but are not limited to, those selected from the group
consisting of quaternary ammonium salts in which at least one
higher molecular weight group and two or three lower molecular
weight groups are linked to a common nitrogen atom to produce a
cation, and wherein the electrically-balancing anion is selected
from the group consisting of a halide (bromide, chloride, etc.),
acetate, nitrite, and lower alkosulfate (methosulfate etc.). The
higher molecular weight substituent(s) on the nitrogen is/are often
(a) higher alkyl group(s), containing about 10 to about 20 carbon
atoms, and the lower molecular weight substituents may be lower
alkyl of about 1 to about 4 carbon atoms, such as methyl or ethyl,
which may be substituted, as with hydroxy, in some instances. One
or more of the substituents may include an aryl moiety or may be
replaced by an aryl, such as benzyl or phenyl.
[0136] In a preferred embodiment of the invention the surfactant
comprises at least one propylene oxide/ethylene oxide block
copolymer, for example such as that supplied by BASF Plc under the
trade name Pluronic P65 or L64 or F68.
[0137] Other Additives
[0138] The hydrogel composition of the present invention may
include one or more additional ingredients, which may be added to
the pre-polymerisation mixture or the polymerised product, at the
choice of the skilled worker. Such additional ingredients are
selected from additives known in the art, including, for example,
water, organic plasticisers, surfactants, polymers, electrolytes,
pH regulators, colorants, chloride sources, bioactive compounds,
personal and body care agents, and mixtures thereof. The polymers
can be natural polymers (e.g. xanthan gum), synthetic polymers
(e.g. polyoxypropylene-polyoxyethylene block copolymer or
poly-(methyl vinyl ether alt maleic anhydride)), or any combination
thereof. By "bioactive compounds" we mean any compound or mixture
included within the hydrogel for some effect it has on living
systems as opposed to the hydrogel, whether the living system be
bacteria or other microorganisms or higher animals such as the
intended user of articles incorporating the hydrogel. A biocidal
biaoactive compound that may particularly be mentioned is citric
acid.
[0139] Additional polymer(s), typically rheology modifying
polymer(s), may be incorporated into the polymerisation reaction
mixture at levels typically up to about 10% by weight of total
polymerisation reaction mixture, e.g. from about 0.2% to about 10%
by weight. Such polymer(s) may include polyacrylamide, poly-NaAMPS,
polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) or
carboxymethyl cellulose.
[0140] A particularly preferred application is in the field of
biomedical skin electrodes. When the hydrogels are intended for use
in conjunction with Ag/AgCl medical electrodes, chloride ions are
required to be present in order for the electrode to function.
Potassium chloride and sodium chloride are commonly used. However
any compound capable of donating chloride ions to the system may be
used, for example, lithium chloride, calcium chloride, magnesium
chloride or ammonium chloride. The amount that should be added is
dependent on the electrical properties required and is typically
about 0.5-8% by weight.
[0141] In general, an electrolyte (e.g. a salt such as a chloride
as mentioned above or another salt such as a nitrate, for example
sodium or calcium nitrate) will need to be included in the
polymerisation reaction mixture in appropriate amounts, when the
process is used to manufacture a hydrogel composition for use in an
electrode.
[0142] The compositions prepared according to the present invention
are used in biomedical electrodes in generally conventional manner,
as will be readily understood by those skilled in this art. Such
biomedical electrodes may include electrodes (suitably in patch
form) for diagnostic, stimulation, therapeutic and electrosurgical
use. The hydrogel compositions according to the present invention
will typically provide good current dispersion over the
skin-electrode interface, leading to potential benefits through
reduction of electrical hot-spots.
[0143] Additional functional ingredients may also incorporated in
the reaction mixture used in the invention, including bioactive
compounds such as antimicrobial agents (e.g. citric acid, stannous
chloride), enzymes, compounds providing a heating or cooling
sensation to a patient's body, dermatologically active compounds
and, for drug delivery applications, pharmaceutically active
agents, the latter being designed to be delivered either passively
(e.g. transdermally) or actively (e.g. iontophoretically) through
the skin.
[0144] For use in pharmaceutical delivery devices for the delivery
of pharmaceuticals or other active agents to or through mammalian
skin, the compositions may optionally contain topical, transdermal
or iontophoretic agents and excipients. The compositions may
contain penetration-enhancing agents to assist the delivery of
water or active agents into the skin. Non-limiting examples of
penetration-enhancing agents for use in such applications include
methyl oleic acid, isopropyl myristate, Azone.TM., Transcutol.TM.
and N-methylpyrrolidone.
[0145] The additional ingredient may comprise an antimicrobial
agent stable against light and radiation, comprising an effective
amount of antimicrobial metal (e.g. silver) ions and stabilizing
halide (e.g. chloride) ions, wherein the halide is present in an
excess (preferably in a substantial molar excess such as around
500-fold excess) with respect to the amount of metal ions.
[0146] The hydrogel composition of the present invention preferably
consists essentially of a cross-linked hydrophilic polymer of a
hydrophilic monomer and optionally one or more comonomer, together
with water and/or one or more organic plasticiser, and optionally
together with one or more additives selected from surfactants,
polymers, pH regulators, electrolytes, chloride sources, bioactive
compounds and mixtures thereof, with less than about 10% by weight
of other additives.
Applications
[0147] The hydrogel compositions described herein may suitably be
used in a range of skin contact or covering applications where the
composition is brought into contact either with skin or with an
intermediary member which interfaces between the composition and
the skin. The composition may be unsupported or may be supported on
a part of a larger article for some specific use, e.g. a backing
structure. The compositions may suitably be in the form of sheets,
coatings, membranes, composites or laminates. Applications include
patches, tapes, bandages, devices and dressings of general utility
or for specific uses, including without limitation biomedical, skin
care, personal and body care, palliative and veterinary uses such
as, for example, skin electrodes for diagnostic (e.g. ECG),
stimulation (e.g. TENS), therapeutic (e.g. defibrillation) or
electrosurgical (e.g. electrocauterisation) use; dressings and
reservoirs for assisting wound and burn healing, wound and burn
management, skin cooling, skin moisturizing, skin warming, aroma
release or delivery, decongestant release or delivery,
pharmaceutical and drug release or delivery, perfume release or
delivery, fragrance release or delivery, scent release or delivery,
and other skin contacting devices such as absorbent pads or patches
for absorbing body fluids (e.g. lactation pads for nursing
mothers), hairpiece adhesives and clothing adhesives; and adhesive
flanges and tabs for fecal collection receptacles, ostomy devices
and other incontinence devices.
EXAMPLES
[0148] The invention will be further described with reference to
the following Examples, which should not be understood to limit the
scope of the invention.
Test Methods
[0149] Pre-foam viscosity was determined using a Brookfield
Viscometer with a S18 spindle in a closed volume at a speed of 20
rpm. The pre-cured foam viscosities were also determined using a
Brookfield Viscometer with a S18 spindle in a closed volume at a
speed of 2 rpm.
[0150] The rate of absorption of water on the continous layer and
on the porous layer were determined by placing a 5 .mu.l drop from
a syringe and monitoring the drop volume on the surface of the
material over the first 0.1 s. This was done using a Scientific and
Medical Products DAT1100 dynamic contact angle analyser.
[0151] The rheology of the hydrogel foam composite was determined
with a Rheometrics SR5 rheometer over a range from 0.1 to 100
rad/s.
[0152] Water activities of the foamed hydrogels were determined
with an AquaLab Series 3TE water activity meter.
Preparative Methods and Compositions
Examples 1 to 15
Preparative Method and Apparatus
[0153] The method for making 200 g of hydrogel foam will be
described below. It will be appreciated by those skilled in the art
that this may be scaled up to enable semi-continuous or continuous
hydrogel foam to be made.
[0154] 200 g of hydrogel pre-foam formulation mix is added to a 500
ml vessel. A paddle stirrer is placed into the pre-foam formulation
mix. The paddle is connected to an IKA RW 16 Basic mixer. The mix
is stirred for three minutes at a speed of 500 to 600 rpm until the
mix is frothy and has increased in viscosity. It will be
appreciated that different mixing times and speeds may be employed
depending on the extent of foaming required. At the end of the
foaming period the paddle is removed from the vessel. The foam is
then poured (cast) onto a suitable substrate surface (e.g. a film,
embossed film, non woven or net substrate, made from natural or
synthetic materials or combinations of both) and irradiated with UV
light (for example from a medium pressure mercury arc lamp) to cure
the foam. The resulting material is according to this invention a
composite structure comprising a continuous hydrogel layer (as
defined above) in contact with the substrate and a porous layer
adjacent to it. By casting the foamed mix onto a moving substrate,
a continuous roll of composite material can be produced at speeds
from 0.5 m/min to 30 m/min. Variation of the extent of foaming and
the time between casting the foam and then curing allows the
thickness ratio of the continuous and porous layer portions of the
hydrogel sheet to be altered and controlled.
Examples 1 to 15
Compositions
[0155] The compositions of the hydrogels prepared are shown below:
TABLE-US-00001 Example Number 1 2 N-Acryloylmorpholine % 0.0 0.0
Sodium 2-acrylamido-2-methylpropane sulphonate % 31.3 56.8
N,N-Dimethylaminoethylacrylate, methyl chloride quarternary salt %
26.2 0.0 N,N-Dimethylamide % 0.0 0.0 3-Sulphopropyl acrylate
potassium salt % 0.0 0.0 Acrylic Acid % 0.0 0.0 Sodium Acrylate %
0.0 0.0 Glycerol % 9.9 0.0 Water % 29.6 41.2 Citric Acid % 0.0 0.0
Silver Nitrate % 0.0 0.0 Magnesium Chloride hexahydrate % 0.0 0.0
Polyoxypropylene-Polyoxyethylene block co-polymer % 3.0 2.0
Daracure 1173/Irgacure 280 15/20 g/100 g 0.0 0.0 Daracure
1173/Irgacure 280 8/20 g/100 g 0.0 0.0 Daracure 1173/Irgacure 280
6/20 g/100 g 0.0 0.0 Daracure 1173/Irgacure 280 4/20 g/100 g 0.7
0.0 Daracure 1173/Irgacure 280 1/20 g/100 g 0.0 0.6 Example Number
3 4 N-Acryloylmorpholine % 48.4 48.0 Sodium
2-acrylamido-2-methylpropane sulphonate % 1.9 1.9
N,N-Dimethylaminoethylacrylate, methyl chloride quarternary salt %
0.0 0.0 N,N-Dimethylamide % 0.0 0.0 3-Sulphopropyl acrylate
potassium salt % 0.0 0.0 Acrylic Acid % 0.0 0.0 Sodium Acrylate %
0.0 0.0 Glycerol % 32.3 32.0 Water % 14.3 14.1 Citric Acid % 0.0
0.8 Silver Nitrate % 0.0 0.0 Magnesium Chloride hexahydrate % 0.0
0.0 Polyoxypropylene-Polyoxyethylene block co-polymer % 3.2 3.2
Daracure 1173/Irgacure 280 15/20 g/100 g 0.0 0.0 Daracure
1173/Irgacure 280 8/20 g/100 g 0.0 0.0 Daracure 1173/Irgacure 280
6/20 g/100 g 1.2 1.2 Daracure 1173/Irgacure 280 4/20 g/100 g 0.0
0.0 Daracure 1173/Irgacure 280 1/20 g/100 g 0.0 0.0 Example Number
5 6 N-Acryloylmorpholine % 28.4 48.7 Sodium
2-acrylamido-2-methylpropane sulphonate % 0 5.7
N,N-Dimethylaminoethylacrylate, methyl chloride quarternary salt %
0 0 N,N-Dimethylamide % 0.0 0 3-Sulphopropyl acrylate potassium
salt % 0.0 0 Acrylic Acid % 0.0 0 Sodium Acrylate % 0.0 0 Glycerol
% 14.3 39 Water % 18.9 4.1 Citric Acid % 0 0 Silver Nitrate % 0.0 0
Magnesium Chloride hexahydrate % 36 0
Polyoxypropylene-Polyoxyethylene block co-polymer % 2.4 2.4
Daracure 1173/Irgacure 280 15/20 g/100 g 0.0 0.4 Daracure
1173/Irgacure 280 8/20 g/100 g 0.1 0.0 Daracure 1173/Irgacure 280
6/20 g/100 g 0.0 0.0 Daracure 1173/Irgacure 280 4/20 g/100 g 0.0
0.0 Daracure 1173/Irgacure 280 1/20 g/100 g 0.0 0.0 Example Number
7 8 N-Acryloylmorpholine % 0.0 0.0 Sodium
2-acrylamido-2-methylpropane sulphonate % 7.6 0.0
N,N-Dimethylaminoethylacrylate, methyl chloride quarternary salt %
0.0 0.0 N,N-Dimethylamide % 0.0 0.0 3-Sulphoproply acrylate
potassium salt % 0.0 0.0 Acrylic Acid % 0.0 0.0 Sodium Acrylate %
25.1 28.5 Glycerol % 0.0 0.0 Water % 64.1 66.8 Citric Acid % 0.0
0.0 Silver Nitrate % 0.0 0.0 Magnesium Chloride hexahydrate % 0.0
0.0 Polyoxypropylene-Polyoxyethylene block co-polymer % 3.3 0.0
Daracure 1173/Irgacure 280 15/20 g/100 g 0.0 0.0 Daracure
1173/Irgacure 280 8/20 g/100 g 0.0 0.0 Daracure 1173/Irgacure 280
6/20 g/100 g 0.0 0.0 Daracure 1173/Irgacure 280 4/20 g/100 g 0.0
0.0 Daracure 1173/Irgacure 280 1/20 g/100 g 0.8 0.7 Example Number
9 10 N-Acryloylmorpholine % 0.00 0.0 Sodium
2-acrylamido-2-methylpropane sulphonate % 56.77 32.8
N,N-Dimethylaminoethylacrylate, methyl chloride quarternary salt %
0.00 0.0 N,N-Dimethylamide % 0.00 0.0 3-Sulphopropyl acrylate
potassium salt % 0.00 9.6 Acrylic Acid % 0.00 1.9 Sodium Acrylate %
0.00 0.0 Glycerol % 0.00 33.7 Water % 41.11 23.0 Citric Acid % 0.00
0.0 Silver Nitrate % 0.01 0.0 Magnesium Chloride hexahydrate % 0.00
0.0 Polyoxypropylene-Polyoxyethylene block co-polymer % 2.11 1.9
Daracure 1173/Irgacure 280 15/20 g/100 g 0.00 0.0 Daracure
1173/Irgacure 280 8/20 g/100 g 0.00 0.0 Daracure 1173/Irgacure 280
6/20 g/100 g 0.00 0.0 Daracure 1173/Irgacure 280 4/20 g/100 g 0.00
0.0 Daracure 1173/Irgacure 280 1/20 g/100 g 0.7 0.1 Example Number
11 112 N-Acryloylmorpholine % 0.0 0.0 Sodium
2-acrylamido-2-methylpropane sulphonate % 0 0
N,N-Dimethylaminoethylacrylate, methyl chloride quarternary salt %
0.0 0.0 N,N-Dimethylamide % 47.5 0.0 3-Sulphopropyl acrylate
potassium salt % 0.0 49.0 Acrylic Acid % 0.0 0.0 Sodium Acrylate %
0.0 0.0 Glycerol % 40.0 24.2 Water % 10.0 24.3 Citric Acid % 0.0
0.0 Silver Nitrate % 0.0 0.0 Magnesium Chloride hexahydrate % 0.0
0.0 Polyoxypropylene-Polyoxyethylene block co-polymer % 2.5 2.5
Daracure 1173/Irgacure 280 15/20 g/100 g 0.0 0.0 Daracure
1173/Irgacure 280 8/20 g/100 g 0.0 0.0 Daracure 1173/Irgacure 280
6/20 g/100 g 0.7 0.0 Daracure 1173/Irgacure 280 4/20 g/100 g 0.0
0.3 Daracure 1173/Irgacure 280 1/20 g/100 g 0.0 0.0 Example Number
13 N-Acryloylmorpholine % 0.0 Sodium 2-acrylamido-2-methylpropane
sulphonate % 0 N,N-Dimethylaminoethylacrylate, methyl chloride
quarternary salt % 28.2 NN Dimethylamide % 0.0 3-Sulphonyl acrylate
potassium salt % 0 Acrylic Acid % 0.0 Sodium Acrylate % 0.0
Glycerol % 47.3 Water % 18.9 Citric Acid % 0.0 Silver Nitrate % 0.0
Magnesium Chloride hexahydrate % 0.0
Polyoxypropylene-Polyoxyethylene block co-polymer % 5.5 Daracure
1173/Irgacure 280 15/20 g/100 g 0.0 Daracure 1173/Irgacure 280 8/20
g/100 g 0.9 Daracure 1173/Irgacure 280 6/20 g/100 g 0.0 Daracure
1173/Irgacure 280 4/20 g/100 g 0.0 Daracure 1173/Irgacure 280 1/20
g/100 g 0.0 Compositions containing thickeners and or fillers
Example Number 14 15 N-Acryloylmorpholine % 0.0 0.0 Sodium
2-acrylamido-2-methylpropane sulphonate % 31.3 34.6
N,N-Dimethylaminoethylacrylate, methyl chloride quarternary salt %
26.2 28.9 Glycerol % 0.0 0.0 Water % 38.5 32.7 Poly (methyl vinyl
ether alt maleic anhydride) % 1.0 0.0 Xanthan gum % 0.0 0.5
Polyoxypropylene-Polyoxyethylene block co-polymer % 3.0 3.3
Daracure 1173/Irgacure 280 15/20 g/100 g 0.0 0.0 Daracure
1173/Irgacure 280 8/20 g/100 g 0.0 0.0 Daracure 1173/Irgacure 280
6/20 g/100 g 0.7 0.7 Daracure 1173/Irgacure 280 4/20 g/100 g 0.0
0.0 Daracure 1173/Irgacure 280 1/20 g/100 g 0.0 0.0
Examples 16 to 49
Preparative Method and Apparatus
[0156] The appropriate weight of N-acryloylmorpholine (ACMO) was
added to the appropriate weight of water (Examples 16 to 37, 39,
40, 45, 46 to 49) or to the aqueous saturated or supersaturated
liquid formed by gentle warming of a hydrated salt (see further
details below) to about 60.degree. C. (Examples 38, 41 to 44, 47
and 48). The surfactant Pluronic 65 ("P65") was added to each
aqueous composition thereby obtained.
[0157] For Examples 33, 34, 41 and 43, acrylic acid (AA) comonomer
was also added with the ACMO. For Example 24,
2-acrylamido-2-methylpropane sulphonic acid sodium salt (NaAMPS)
was also added with the ACMO (see discussion below). For Examples
39, 40, 45 and 47 to 49, a salt (see further details below) was
also added, if necessary with gentle warming. For Examples 38 to
49, the salt was selected from calcium chloride hexahydrate
(Examples 38 to 43), calcium nitrate tetrahydrate (Examples 44 and
45), a 50:50 weight mixture of calcium chloride hexahydrate and
calcium nitrate tetrahydrate (Example 46), sodium chloride (Example
47) and magnesium chloride hexahydrate (Examples 48 and 49). The
amounts of the AA and the salt are indicated in the table below.
The appropriate weight of glycerol was added (Examples 20 to 30, 33
to 37, 42 and 43 only) and the mixture stirred for about 30
minutes. Amounts of these initial ingredients for Examples 16 to 37
are shown in parts by weight (normally out of 100, but out of 104
in the case of Example 24); amounts for Examples 38 to 49 are shown
in grams.
[0158] A mixture of crosslinker ("XL") and photoinitiator ("PI")
was made by adding the appropriate weight of IRR280 (PEG400
diacrylate, UCB Chemicals) ("280") to the appropriate weight of
photoinitiator, Daracur 1173 (Ciba Specialty Chemicals) ("1173")".
The appropriate amount of this liquid mixture was added to the
mixture, which was stirred for 1 hour, covered to exclude light.
The figures for Examples 16 to 24, 27 and 31 to 35 in the table
below show the percentage by weight of the initial mixture, at
which the PI/XL mixture (6 parts by weight PI: 20 parts by weight
XL) is added. The figures for Examples 25, 36 and 37 in the table
below show the percentage by weight of the initial mixture, at
which the PI/XL mixture (10 parts by weight PI: 20 parts by weight
XL) is added. The figure for Example 26 in the table below shows
the percentage by weight of the initial mixture, at which the PI/XL
mixture (100.7 parts by weight PI: 108 parts by weight XL) is
added. The figure for Example 28 in the table below shows the
percentage by weight of the initial mixture, at which the PI/XL
mixture (I parts by weight PI: 3 parts by weight XL) is added. The
figure for Example 29 in the table below shows the percentage by
weight of the initial mixture, at which the PI/XL mixture (9 parts
by weight PI: 10 parts by weight XL) is added. The figure for
Example 30 in the table below shows the percentage by weight of the
initial mixture, at which the PI/XL mixture (35 parts by weight PI:
54 parts by weight XL) is added. The figures for Examples 38 to 49
in the table below show the weight of the PI/XL mixture (1 parts by
weight PI: 10 parts by weight XL) added.
[0159] In each case the mixture was mechanically agitated with a
high speed stirrer, to entrain air bubbles in the pre-gel. 50 g of
the mixture was then cast on a tray lined with siliconised paper at
a coat weight of 1.5 kg/sq.m and was cured in the laboratory by
passing at a speed of 7 m/minute three times under ultra-violet
(UV) radiation of 80 W/cm from a medium pressure mercury vapour
lamp. The resultant cured hydrogel mass had an internal cellular
structure, caused by the presence of the air bubbles.
Example 16 to 49
Compositions
[0160] The ingredients of the compositions of Examples 16 to 49 are
shown in the following table: TABLE-US-00002 Ex.16 Ex.17 Ex.18
Ex.19 Ex.20 Ex.21 Ex.22 Ex.23 Ex.24 ACMO 35 35 35 35 35 35 35 35 35
Water 65 65 65 65 50 30 20 10 10 Glycerol 0 0 0 0 15 35 45 55 55
PI/XL 0.1 0.2 0.3 0.4 0.4 0.4 0.4 0.4 0.4 NaAMPS 0 0 0 0 0 0 0 0 4
P65 2 2 2 2 2 2 2 2 2 Ex.25 Ex.26 Ex.27 Ex.28 Ex.29 Ex.30 Ex.31
Ex.32 ACMO 35 35 35 35 35 35 20 20 Water 20 20 20 20 20 20 80 80
Glycerol 45 45 45 45 45 45 0 0 PI/XL 0.3 0.21 0.147 0.41 0.18 0.16
0.30 0.40 P65 2 2 2 2 2 2 2 2 Ex.33 Ex.34 Ex.35 Ex.36 Ex.37 Ex.38
Ex.39 Ex.40 ACMO 30 30 35 35 35 1.5 g 1.5 g 2 g Water 28 28 20 20
20 0 g 2 g 8 g Glycerol 40 40 45 45 45 0 g 0 g 0 g PI/XL 0.35 0.25
0.40 0.30 0.15 0.03 g 0.03 g 0.03 g AA 2 2 0 0 0 0 g 0 g 0 g Salt 0
0 0 0 0 10 g 8 g 2 g P65 2 2 2 2 2 0.2 g 0.2 g 0.2 g Ex.41 Ex.42
Ex.43 Ex.44 Ex.45 Ex.46 Ex.47 Ex.48 Ex.49 ACMO 1 g 1.5 g 2.5 g 1.5
g 1.5 g 1.5 g 2 g 1.5 g 1.5 g Water 0 g 0 g 0 g 0 g 2 g 0 g 8 g 3 g
2.3 g Glycerol 0 g 0.75 g 1.5 g 0 g 0 g 0 g 0 g 0 g 0 g PI/XL 0.03
g 0.03 g 0.03 g 0.03 g 0.03 g 0.03 g 0.03 g 0.03 g 0.03 g AA 0.5 g
0 g 0.5 g 0 g 0 g 0 g 0 g 0 g 0 g Salt 10 g 10 g 20 g 10 g 8 g 10 g
2 g 7 g 7.7 g P65 0.2 g 0.2 g 0.1 g 0.2 g 0.2 g 0.2 g 0.2 g 0.2 g
0.2 g
Example 50
Preparative Method and Composition
[0161] 40.84 g of a 58% aqueous solution of NaAMPS (Lubrizol) were
mixed with 25 g of a 79% aqueous solution of
acryloyloxyethyltrimethyl ammonium chloride (DMAEA-Q (Kohjin)) and
34.16 g of glycerol for 30 minutes and 3 g of Pluronic P65 (Ciba
Geigy). To this mixture 0.19 g of a Daracur 1173 photoinitiator (4
parts) and polyethylene glycol diacrylate (IRR 280, UCB)(20 parts)
solution was added and stirred for 30 mintutes. The mixture was
mechanically agitated to produce foamed liquid and then coated on
to a siliconised polyester backing and passed under a UV lamp. The
mixture cured rapidly to produce a gel with good tack and adhesion
properties.
Examples 51 to 57
Preparative Methods
Non-z-Swelling Foam Structures
[0162] The exemplified methods of making z-swelling-restricted
porous hydrogels of the present invention involve control of the
method of making the foam and the nature of the surfactant or
mixtures of surfactants used. For a given surfactant, for example
polyoxypropylene-polyoxyethylene block copolymer surfactants such
as F68 or P65, available from BASF, the higher the speed of mixing
the greater the level of closed cell porous hydrogel relative to
open cell. If the mixer speed, is not sufficient then only open
cell materials are made.
Blending
[0163] 1. Foams Containing F68 as Surfactant
[0164] A pre-mix of the crosslinker and the photoiniator was made
by adding 20 g of Irgacure 280 to 1 g of Daracure 1173. This was
stirred in the dark for at least 1 hour. Once made, this mixture
can be stored in the dark for several weeks.
[0165] The F68 and any P65 (melted) required were weighed out into
a dry beaker of appropriate size for foaming. The required amount
the Daracure 1173 and Irgacure 280 pre-mix were then added,
followed by the monomer, and then glycerol or other humectant(s).
The mixture was then stirred in the dark until the F68 surfactant
had dissolved. After the surfactant had dissolved the magnetic
stirring bar was removed and the mixture foamed using one of the
methods described below (as stated in the tables below).
[0166] 2. Foams Containing P65 as Surfactant
[0167] A pre-mix of the Daracure 1173 and Irgacure wass made by
adding 20 g of Irgacure 280 to 1 g of Daracure 1173. This was
stirred in the dark for at least 1 hour. Once made, this mixture
can be stored in the dark for several weeks.
[0168] The required amount of Daracure 1173 and Irgacure 280
pre-mix was weighed into a dry vessel of appropriate size for
foaming. The required amount of melted P65 surfactant was then
added, followed by the monomer and the glycerol (or other
humectants). The mixture was then foamed using one of the methods
described below (as stated in the tables below).
Foaming
[0169] Propellor Method
[0170] Approximately 50 g of the polymerisable mixture is weighed
into a 100 ml jar. A propeller mixer is then used to stir the
mixture at high speed (setting 10 on a RW16 Basic mixer from IKA
Labortechnik; this equates to approximately 1200 rpm) for 3 minutes
until the mixture is white with the texture of double cream. The
mixture will appear smooth and even with no large bubbles on the
surface on the mixture. The foamed mixture is poured out and cured
with UV light.
[0171] Paddle Stirrer at High Speed
[0172] Approximately 100 g of polymerisable mixture is weighed into
a 600 ml beaker. A paddle stirrer is then used to stir the mixture
at high speed (setting 7 on a RW16 Basic mixer from IKA
Labortechnik, this equates to approximately 800 rpm) for 3 minutes
until the mixture is white with the texture of double cream. The
mixture will appear smooth and even, with no large bubbles on the
surface on the mixture. The foamed mixture is poured out and cured
with UV light.
[0173] Paddle Stirrer at Intermediate Speed with Different
Surfactant Systems
[0174] Approximately 100 g of polymerisable mixture comprising F68
as a surfactant (Examples 51 and 52) is weighed into a 600 ml
beaker. A paddle stirrer is then used to stir the mixture at
intermediate speed (setting 5 on a RW16 Basic mixer from IKA
Labortechnik this equates to 550 rpm) for 3 minutes until the
mixture is white with the texture of double cream. The mixture will
appear smooth and even, with no large bubbles on the surface on the
mixture. The foamed mixture is poured out and cured with UV
light.
[0175] Approximately 100 g of polymerisable mixture comprising P65
as a surfactant (Example 57) is weighed into a 600 ml beaker. A
paddle stirrer is then used to stir the mixture at intermediate
speed (setting 5 on a RW16 Basic mixer from IKA Labortechnik, this
equates to 550 rpm) for 3 minutes until the mixture is white with
the texture of double cream. The mixture will appear white and
bubbly; there may be some large bubbles on the surface on the
mixture. The foamed mixture is poured out and cured with UV
light.
Examples 51 to 57
Compositions
[0176] TABLE-US-00003 EXAMPLE 51 52 53 2-Acrylamido-2-methylpropane
sulphonic acid, g 36.6 37.1 37.1 sodium salt Water g 26.5 26.9 26.9
Glycerol g 34.1 34.6 34.6 Polyoxypropylene-polyoxyethylene block
copolymer, g 0 0 0.5 P65 Polyoxypropylene-polyoxyethylene block
copolymer, g 2.8 1.4 0.9 F68 Daracure 1173 g/100 g 0.025 0.026
0.026 Irgacure 280 g/100 g 0.507 0.514 0.515 Mix Method Paddle
Paddle Paddle Mix Time Mins 3 3 3 mixer Mix Speed setting 5 5 5
EXAMPLE 54 55 56 2-Acrylamido-2-methylpropane sulphonic acid, g
37.1 38 38 sodium salt Water g 26.9 27.6 27.6 Glycerol g 34.6 33 33
Polyoxypropylene-polyoxyethylene block copolymer, g 1 1.4 1.4 P65
Polyoxypropylene-polyoxyethylene block copolymer, g 0.5 0 0 F68
Daracure 1173 g/100 g 0.025 0.02 0.02 Irgacure 280 g/100 g 0.507
0.538 0.538 Mix Method Paddle Paddle Propellor Mix Time mins 3 3 3
mixer Mix Speed setting 5 7 10 EXAMPLE 57
2-Acrylamido-2-methylpropane sulphonic acid, sodium salt g 38 Water
g 27.6 Glycerol g 33 Polyoxypropylene-polyoxyethylene block
copolymer, P65 g 1.4 Polyoxypropylene-polyoxyethylene block
copolymer, F68 g 0 Daracure 1173 g/100 g 0.025 Irgacure 280 g/100 g
0.507 Mix Method Paddle Mix Time mins 3 mixer Mix Speed setting
2
Results and Discussion
Examples 1 to 6
Test Results and Discussion
[0177] Certain physical parameters of the compositions prepared in
Examples 1 to 6 were tested using the test methods described above.
The results are shown below (Aw=water activity): TABLE-US-00004
Cured Foam Water Cured Foam Foam Absorption Water Pre-Foam Pre-Cure
Continuous Absorption Viscosity Viscosity Layer Porous Layer
Example (mPas) (mPas) (microl/s) (microl/s) 1 33 324 0 5 2 28 878
0.1 4 3 40 640 0 25 4 29 465 5 13 5 Na Na 1 4 6 Na Na 0 3 Cured
Foam Cured Foam Cured Foam Viscous Elastic Elastic Modulus modulus
@1 Modulus@100 @1 (rad/s) Example (rad/s) (Pa) (rad/s) (Pa) (Pa) Aw
1 8887 13730 1487 0.74 2 8197 16666 2636 0.78 3 1688 3305 467 0.48
4 1567 3714 535 0.48 5 5062 10386 1383 0.46 6 14479 99239 9698
0.27
[0178] In all of Examples 1 to 15, the foamed hydrogels produced
were acceptable gels having good to excellent water uptake rate on
the porous side. In the Examples tested (Examples 1 to 6), the
foamed hydrogels had acceptable water activity, elastic and viscous
moduli for use in the applications described above.
Examples 16 to 49
Results and Discussion
[0179] Example 16 gave a gel which was clear and colourless, soft
and leggy. Example 17 gave a gel which was clear and colourless, a
nice soft gel. Example 18 gave a gel which was clear, colourless
and tough. Example 19 gave a gel which was clear and colourless, a
tough and brittle gel. Example 20 gave a gel which was clear and
colourless, tough and slightly tacky. Examples 21 and 22 gave gels
which were clear and colourless, tough and tacky. All the above
gels were acceptable.
[0180] Example 23 gave a gel which was white, hard and brittle and
showed syneresis of the glycerol. This gel was unacceptable for use
as a bioadhesive. It is believed that this unacceptability may be
more generally observed at very high levels of organic plasticiser.
However, as shown by Example 24, the problem is surprisingly and
effectively overcome by the presence of a small amount of the ionic
comonomer (N PS) in the pre-gel. Example 24 gave an acceptable
clear, colourless, tough gel.
[0181] Example 25 gave a gel which was clear and colourless, soft
and tacky. Examples 26 and 27 gave gels which were leggy. Example
28 gave a gel which was clear and colourless, tough, tacky and
brittle. Examples 29 and 30 gave clear leggy gels. Example 31 gave
a gel which was soft, clear and leggy. Example 32 gave a gel which
was clear but brittle. Example 33 gave a gel which was clear and
strong. Example 34 gave a gel which was clear but soft. Examples 35
to 37 gave gels which were clear and slightly tacky. Examples 38 to
49 gave acceptable gels, many of which displayed substantial
robustness under extremes of temperature and atmospheric dryness.
In summary, all of Examples 25 to 49 produced acceptable gels.
Example 50
Results and Discussion
[0182] The polymerisable mixture cured rapidly to produce a gel
with good tack and adhesion properties. The gel has low saline
uptake compared to gel made using the same method but replacing the
DMAEA-Q with NaAMPS.
Examples 51 to 57
Results and Discussion
[0183] Examples 51 to 56 all gave foamed porous hydrogels having
substantially no z-swelling on exposure to external water. Example
57 showed some degree of z-swelling.
INDUSTRIAL APPLICABILITY
[0184] The present invention makes available porous hydrogels with
useful capacity to absorb potentially large quantities of liquids
at an acceptable speed for many uses. Moreover, the hydrogels can
be made conveniently and efficiently. The process can be such that
polymerisation of the polymerisable (pre-gel) mixture is
substantially the final processing step in the hydrogel
manufacture, with no or only very trivial post-processing of the
hydrogel being required. Alternatively, the porosity of the
hydrogel can make it attractive to load additional components into
the porous structure after initial polymerisation, preferably on
the same support arrangement on which the polymerisable mixture was
laid down before polymerisation, thereby reducing manufacturing
complexity and the risk of contamination through handling.
[0185] The present invention has been broadly described without
limitation. Variations and modifications as will be readily
apparent to those skilled in the art are intended to be covered by
the present application and resultant patent(s).
* * * * *